Ignet

Gene Information

Gene symbol: NMB

Gene name: neuromedin B

HGNC ID: 7842

Synonyms: MGC2277, MGC3936, MGC17211

Related Genes

#	Gene Symbol	Number of hits
1	BRS3	1 hits
2	CALCA	1 hits
3	CDKN1A	1 hits
4	EDN1	1 hits
5	GAL	1 hits
6	GAST	1 hits
7	GNAS	1 hits
8	GPLD1	1 hits
9	GRP	1 hits
10	GRPR	1 hits
11	IGKV1-22	1 hits
12	IKBKG	1 hits
13	NMBR	1 hits
14	NPY	1 hits
15	NTS	1 hits
16	OPRM1	1 hits
17	PLAT	1 hits
18	PLCB1	1 hits
19	PLCG1	1 hits
20	PTK2	1 hits
21	SEC23IP	1 hits
22	SST	1 hits
23	TAC1	1 hits
24	TSHB	1 hits
25	VIP	1 hits

Related Sentences

#	PMID	Sentence
1	1310640	Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%.
2	1310640	Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP.
3	1310640	These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.
4	1310640	Receptors for vasoactive intestinal peptide (VIP) and muscarinic cholinergic agents occurred on 60%, bombesin and gastrin on 30%, beta-adrenergic agents and gastrin-releasing peptide (GRP) on 20%, and somatostatin, opiates, neuromedin B, and substance P on 10%.
5	1310640	Inhibition of binding by agonists revealed relative potencies of 125I-[Tyr4]bombesin greater than GRP much greater than neuromedin B, and two recently described antagonists were similar in potency to GRP.
6	1310640	These results demonstrate the presence of several different receptors for gastrointestinal hormones or neurotransmitters, some described for the first time, on human colon cancer cell lines, including bombesin-related peptides, VIP, somatostatin, substance P, beta-adrenergic agents, calcitonin gene-related peptide, gastrin, muscarinic cholinergic agents, and opiates.
7	1336112	The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system.
8	1336112	NMB inhibited binding of 125I-[D-Tyro]NMB with high affinity in transfected cells (Ki = 3.08 +/- 0.14 nM) and in C6 cells (Ki = 1.90 +/- 1.10 nM), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type.
9	1336112	The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of 125I-[D-Tyro]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells.
10	1336112	Inositol phosphates were increased in a dose-dependent fashion, with similar half-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nM; C6, 2.09 +/- 0.15 nM) and for the GRP analogue (transfected, 1855 +/- 140 nM; C6, 2129 +/- 250 nM).
11	1336112	These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+.
12	1336112	The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system.
13	1336112	NMB inhibited binding of 125I-[D-Tyro]NMB with high affinity in transfected cells (Ki = 3.08 +/- 0.14 nM) and in C6 cells (Ki = 1.90 +/- 1.10 nM), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type.
14	1336112	The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of 125I-[D-Tyro]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells.
15	1336112	Inositol phosphates were increased in a dose-dependent fashion, with similar half-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nM; C6, 2.09 +/- 0.15 nM) and for the GRP analogue (transfected, 1855 +/- 140 nM; C6, 2129 +/- 250 nM).
16	1336112	These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+.
17	1336112	The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system.
18	1336112	NMB inhibited binding of 125I-[D-Tyro]NMB with high affinity in transfected cells (Ki = 3.08 +/- 0.14 nM) and in C6 cells (Ki = 1.90 +/- 1.10 nM), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type.
19	1336112	The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of 125I-[D-Tyro]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells.
20	1336112	Inositol phosphates were increased in a dose-dependent fashion, with similar half-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nM; C6, 2.09 +/- 0.15 nM) and for the GRP analogue (transfected, 1855 +/- 140 nM; C6, 2129 +/- 250 nM).
21	1336112	These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+.
22	1336112	The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system.
23	1336112	NMB inhibited binding of 125I-[D-Tyro]NMB with high affinity in transfected cells (Ki = 3.08 +/- 0.14 nM) and in C6 cells (Ki = 1.90 +/- 1.10 nM), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type.
24	1336112	The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of 125I-[D-Tyro]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells.
25	1336112	Inositol phosphates were increased in a dose-dependent fashion, with similar half-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nM; C6, 2.09 +/- 0.15 nM) and for the GRP analogue (transfected, 1855 +/- 140 nM; C6, 2129 +/- 250 nM).
26	1336112	These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+.
27	1336112	The receptor that interacts with the mammalian bombesin-related peptide neuromedin B (NMB) is ubiquitous in the gastrointestinal tract and central nervous system.
28	1336112	NMB inhibited binding of 125I-[D-Tyro]NMB with high affinity in transfected cells (Ki = 3.08 +/- 0.14 nM) and in C6 cells (Ki = 1.90 +/- 1.10 nM), whereas the bombesin-related agonists gastrin-releasing peptide (GRP) and [D-Phe6, D-Ala11, Leu14]bombesin(6-16) (GRP analogue) had 100- and 300-fold lower affinities, respectively, for NMB receptors in either cell type.
29	1336112	The nonhydrolyzable guanosine analogue guanosine 5'-(beta,gamma-imido)triphosphate was equipotent in causing a decrease in binding of 125I-[D-Tyro]NMB due to decreased receptor affinity in both cell types, without a change in receptor number, demonstrating that the NMB receptor remained coupled to a guanine nucleotide-binding protein in both native and transfected cells.
30	1336112	Inositol phosphates were increased in a dose-dependent fashion, with similar half-maximal values being obtained for NMB in both cell types (transfected, 1.01 +/- 0.09 nM; C6, 2.09 +/- 0.15 nM) and for the GRP analogue (transfected, 1855 +/- 140 nM; C6, 2129 +/- 250 nM).
31	1336112	These data demonstrate that activation of the receptor for NMB stimulates phospholipase C and increases intracellular Ca2+.
32	1706545	Bombesin and the mammalian-related peptides gastrin-releasing peptide (GRP), GRP and neuromedin B have been shown to have numerous actions in the CNS, gastrointestinal tract and on growth.
33	1708135	Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of 125I-GRP to and in stimulating amylase release from mouse pancreatic acini.
34	1708135	Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN.
35	1708135	Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of 125I-GRP to and in stimulating amylase release from mouse pancreatic acini.
36	1708135	Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN.
37	1720364	In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls.
38	1720364	The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted.
39	1720364	NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally.
40	1943736	Hypothalamic tissue levels of nine regulatory peptides (bombesin, calcitonin gene-related peptide [CGRP], galanin, neuromedin B, neuropeptide Y [NPY], neurotensin, somatostatin, substance P, and vasoactive intestinal peptide [VIP]) were compared in Aston obese diabetic (ob/ob) and lean (+/?)
41	2539739	Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.
42	2539739	To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas.
43	2539739	In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae.
44	2539739	In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B.
45	2539739	Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin.
46	2539739	In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
47	2539739	Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.
48	2539739	To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas.
49	2539739	In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae.
50	2539739	In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B.
51	2539739	Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin.
52	2539739	In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
53	2539739	Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.
54	2539739	To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas.
55	2539739	In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae.
56	2539739	In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B.
57	2539739	Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin.
58	2539739	In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
59	2539739	Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.
60	2539739	To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas.
61	2539739	In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae.
62	2539739	In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B.
63	2539739	Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin.
64	2539739	In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
65	2539739	Neuromedin B receptor in esophagus: evidence for subtypes of bombesin receptors.
66	2539739	To identify receptors for bombesin-related peptides in the rat esophagus, we measured binding of 125I-Bolton-Hunter neuromedin B (125I-BH-neuromedin B) and 125I-[Tyr4]bombesin to tissue sections from the rat esophagus and compared the results with those for rat pancreas.
67	2539739	In the esophagus, the relative potencies for inhibition of binding of both tracers were as follows: neuromedin B greater than bombesin greater than GRP = neuromedin C; similar relative potencies were found for causing contraction of muscle strips from whole esophagus and from the isolated muscularis mucosae.
68	2539739	In pancreas tissue sections and dispersed acini, the relative potencies for inhibition of binding of 125I-[Tyr4]bombesin were as follows: bombesin greater than GRP = neuromedin C much greater than neuromedin B.
69	2539739	Furthermore, this study shows that the esophageal bombesin receptors represent a previously unidentified class of bombesin receptors in that they have a higher affinity for neuromedin B than for bombesin.
70	2539739	In contrast, the pancreatic bombesin receptors have, like all other bombesin receptors described to date, a high affinity for bombesin, but low affinity for neuromedin B.
71	3289997	Hypothalamic concentrations of the other six peptides examined (bombesin, galanin, neuromedin B, substance P, somatostatin, and vasoactive intestinal peptide) did not differ significantly between STZ-D and control groups at any time.
72	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
73	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
74	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
75	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
76	7562561	All of these antagonists had low affinity for the NMB receptor.
77	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
78	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
79	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
80	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
81	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
82	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
83	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
84	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
85	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
86	7562561	All of these antagonists had low affinity for the NMB receptor.
87	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
88	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
89	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
90	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
91	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
92	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
93	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
94	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
95	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
96	7562561	All of these antagonists had low affinity for the NMB receptor.
97	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
98	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
99	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
100	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
101	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
102	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
103	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
104	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
105	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
106	7562561	All of these antagonists had low affinity for the NMB receptor.
107	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
108	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
109	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
110	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
111	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
112	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
113	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
114	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
115	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
116	7562561	All of these antagonists had low affinity for the NMB receptor.
117	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
118	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
119	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
120	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
121	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
122	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
123	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
124	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
125	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
126	7562561	All of these antagonists had low affinity for the NMB receptor.
127	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
128	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
129	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
130	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
131	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
132	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
133	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
134	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
135	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
136	7562561	All of these antagonists had low affinity for the NMB receptor.
137	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
138	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
139	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
140	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
141	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
142	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
143	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
144	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
145	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
146	7562561	All of these antagonists had low affinity for the NMB receptor.
147	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
148	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
149	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
150	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
151	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
152	7562561	Recently it has been established that both a gastrin-releasing peptide (GRP) receptor and a neuromedin B (NMB) receptor mediate the actions of bombesin-related peptides in mammals.
153	7562561	Five different classes of peptides that function as GRP receptor antagonists have been identified; however, it is unknown whether similar strategies will yield antagonists for the closely related NMB receptor.
154	7562561	In the present study we have used either native cells possessing only one bombesin (Bn) receptor subtype or cells stably transfected with one subtype to determine whether using the strategies that were used successfully for GRP receptors would allow NMB receptor antagonists to be identified.
155	7562561	[DPhe12]Bn analogs; des Met14 amides, esters and alkylamides; psi 13-14 Bn pseudopeptides; and D-amino acid-substituted analogs of substance P (SP) or SP(4-11) were all synthesized and each functioned as a GRP receptor antagonist.
156	7562561	All of these antagonists had low affinity for the NMB receptor.
157	7562561	Application of similar strategies to NMB by formation of [DPhe8]NMB, [psi 9-10]NMB pseudopeptides, des-Met10 NMB amides, alkylamide or esters did not result in any potent NMB receptor antagonists.
158	7562561	D-Amino acid SP and SP(4-11) analogs were weakly selective NMB receptor antagonists.
159	7562561	No COOH-terminal fragments of NMB or GRP functioned as a GRP or NMB receptor antagonist.
160	7562561	These results demonstrate that none of the known strategies used to prepare peptide GRP receptor antagonists are successful at the NMB receptor, suggesting that a different strategy will be needed for this peptide, such as the formation of somatostatin octapeptide or D-amino acid-substituted substance P analogs.
161	7562561	These results suggest that even though there is a close homology between GRP and NMB and their receptors, their structure-function relations are markedly different.
162	7651888	Bombesin (BN)-related peptides, such as gastrin-releasing peptide (GRP), have been shown in vivo to stimulate release of pepsinogen.
163	7651888	BN, GRP, or neuromedin B (NMB), at concentrations up to 1 microM, did not stimulate pepsinogen release or affect the stimulation caused by vasoactive intestinal peptide (VIP) (100 nM) or CCK-8 (10 nM), respectively.
164	7651888	In addition, BN, GRP, or NMB at a concentration of 1 microM did not increase cAMP nor did they alter the increase in cAMP caused by VIP or secretin.
165	7651888	Furthermore, BN, GRP, or NMB at a concentration of 1 microM did not increase the generation of inositol phosphates (IP) or alter the increase in [3H]IP1, [3H]IP2, or [3H]IP3, caused by CCK-8 (1 microM) or carbachol (1 mM).
166	7651888	Bombesin (BN)-related peptides, such as gastrin-releasing peptide (GRP), have been shown in vivo to stimulate release of pepsinogen.
167	7651888	BN, GRP, or neuromedin B (NMB), at concentrations up to 1 microM, did not stimulate pepsinogen release or affect the stimulation caused by vasoactive intestinal peptide (VIP) (100 nM) or CCK-8 (10 nM), respectively.
168	7651888	In addition, BN, GRP, or NMB at a concentration of 1 microM did not increase cAMP nor did they alter the increase in cAMP caused by VIP or secretin.
169	7651888	Furthermore, BN, GRP, or NMB at a concentration of 1 microM did not increase the generation of inositol phosphates (IP) or alter the increase in [3H]IP1, [3H]IP2, or [3H]IP3, caused by CCK-8 (1 microM) or carbachol (1 mM).
170	7651888	Bombesin (BN)-related peptides, such as gastrin-releasing peptide (GRP), have been shown in vivo to stimulate release of pepsinogen.
171	7651888	BN, GRP, or neuromedin B (NMB), at concentrations up to 1 microM, did not stimulate pepsinogen release or affect the stimulation caused by vasoactive intestinal peptide (VIP) (100 nM) or CCK-8 (10 nM), respectively.
172	7651888	In addition, BN, GRP, or NMB at a concentration of 1 microM did not increase cAMP nor did they alter the increase in cAMP caused by VIP or secretin.
173	7651888	Furthermore, BN, GRP, or NMB at a concentration of 1 microM did not increase the generation of inositol phosphates (IP) or alter the increase in [3H]IP1, [3H]IP2, or [3H]IP3, caused by CCK-8 (1 microM) or carbachol (1 mM).
174	7794919	Characterization of gastrin-releasing peptide receptor expressed in Sf9 insect cells by baculovirus.
175	7794919	Whereas baculovirus expression systems have been extensively used for high-level expression of steroid receptors and receptors coupled to adenylate cyclase, there are few studies on peptide receptors coupled to phospholipase C (PLC).
176	7794919	In the present study we have expressed the murine gastrin-releasing peptide receptor (mGRP-R) in Sf9 cells using a recombinant baculovirus and characterized it structurally and functionally. mGRP-R was detectible 12 h post infection with recombinant baculovirus carrying mGRP-R cDNA and became maximal at 60 h post infection (Bmax = 6 pmol/mg protein), which is a 4-60-fold greater density than is found in native tissues.
177	7794919	In binding studies the affinity of the mGRP-r in Sf9 cells for the agonists bombesin (Bn), GRP, and neuromedin B (NMB) varied differently with infection time: with Bn the affinity decreased 3-fold with longer infection times, with GRP it remained unchanged, and with NMB it decreased 10-fold.
178	7838118	Human gastrin-releasing peptide (GRP) receptors (huGRP-R) and human neuromedin B (NMB) receptors (huNMB-R) were stably transfected into BALB/3T3 fibroblasts.
179	7838118	The affinities of various agonists for binding to the huGRP-R were Bn (Ki = 1.4 +/- 0.2 nM) = 4 x GRP = 300 x NMB.
180	7838118	In contrast, affinities for the huNMB-R were NMB (Ki = 8.1 +/- 5.2 nM) = 4 x Bn = 600 x GRP.
181	7838118	GRP was potent at increasing [3H]inositol phosphate generation in cells expressing the huGRP-R (EC50 = 13.6 +/- 1.3 nM), whereas NMB was similarly potent when acting upon cells expressing the huNMB-R (EC50 = 9.3 +/- 1.4 nM).
182	7838118	Minimal native huNMB-R data are available for comparison, but in general the huNMB-R is similar to the rat NMB receptor in its pharmacology and cell biology.
183	7838118	Human gastrin-releasing peptide (GRP) receptors (huGRP-R) and human neuromedin B (NMB) receptors (huNMB-R) were stably transfected into BALB/3T3 fibroblasts.
184	7838118	The affinities of various agonists for binding to the huGRP-R were Bn (Ki = 1.4 +/- 0.2 nM) = 4 x GRP = 300 x NMB.
185	7838118	In contrast, affinities for the huNMB-R were NMB (Ki = 8.1 +/- 5.2 nM) = 4 x Bn = 600 x GRP.
186	7838118	GRP was potent at increasing [3H]inositol phosphate generation in cells expressing the huGRP-R (EC50 = 13.6 +/- 1.3 nM), whereas NMB was similarly potent when acting upon cells expressing the huNMB-R (EC50 = 9.3 +/- 1.4 nM).
187	7838118	Minimal native huNMB-R data are available for comparison, but in general the huNMB-R is similar to the rat NMB receptor in its pharmacology and cell biology.
188	7838118	Human gastrin-releasing peptide (GRP) receptors (huGRP-R) and human neuromedin B (NMB) receptors (huNMB-R) were stably transfected into BALB/3T3 fibroblasts.
189	7838118	The affinities of various agonists for binding to the huGRP-R were Bn (Ki = 1.4 +/- 0.2 nM) = 4 x GRP = 300 x NMB.
190	7838118	In contrast, affinities for the huNMB-R were NMB (Ki = 8.1 +/- 5.2 nM) = 4 x Bn = 600 x GRP.
191	7838118	GRP was potent at increasing [3H]inositol phosphate generation in cells expressing the huGRP-R (EC50 = 13.6 +/- 1.3 nM), whereas NMB was similarly potent when acting upon cells expressing the huNMB-R (EC50 = 9.3 +/- 1.4 nM).
192	7838118	Minimal native huNMB-R data are available for comparison, but in general the huNMB-R is similar to the rat NMB receptor in its pharmacology and cell biology.
193	7838118	Human gastrin-releasing peptide (GRP) receptors (huGRP-R) and human neuromedin B (NMB) receptors (huNMB-R) were stably transfected into BALB/3T3 fibroblasts.
194	7838118	The affinities of various agonists for binding to the huGRP-R were Bn (Ki = 1.4 +/- 0.2 nM) = 4 x GRP = 300 x NMB.
195	7838118	In contrast, affinities for the huNMB-R were NMB (Ki = 8.1 +/- 5.2 nM) = 4 x Bn = 600 x GRP.
196	7838118	GRP was potent at increasing [3H]inositol phosphate generation in cells expressing the huGRP-R (EC50 = 13.6 +/- 1.3 nM), whereas NMB was similarly potent when acting upon cells expressing the huNMB-R (EC50 = 9.3 +/- 1.4 nM).
197	7838118	Minimal native huNMB-R data are available for comparison, but in general the huNMB-R is similar to the rat NMB receptor in its pharmacology and cell biology.
198	7838118	Human gastrin-releasing peptide (GRP) receptors (huGRP-R) and human neuromedin B (NMB) receptors (huNMB-R) were stably transfected into BALB/3T3 fibroblasts.
199	7838118	The affinities of various agonists for binding to the huGRP-R were Bn (Ki = 1.4 +/- 0.2 nM) = 4 x GRP = 300 x NMB.
200	7838118	In contrast, affinities for the huNMB-R were NMB (Ki = 8.1 +/- 5.2 nM) = 4 x Bn = 600 x GRP.
201	7838118	GRP was potent at increasing [3H]inositol phosphate generation in cells expressing the huGRP-R (EC50 = 13.6 +/- 1.3 nM), whereas NMB was similarly potent when acting upon cells expressing the huNMB-R (EC50 = 9.3 +/- 1.4 nM).
202	7838118	Minimal native huNMB-R data are available for comparison, but in general the huNMB-R is similar to the rat NMB receptor in its pharmacology and cell biology.
203	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
204	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
205	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
206	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
207	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
208	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
209	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
210	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
211	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
212	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
213	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
214	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
215	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
216	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
217	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
218	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
219	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
220	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
221	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
222	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
223	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
224	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
225	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
226	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
227	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
228	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
229	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
230	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
231	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
232	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
233	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
234	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
235	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
236	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
237	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
238	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
239	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
240	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
241	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
242	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
243	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
244	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
245	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
246	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
247	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
248	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
249	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
250	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
251	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
252	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
253	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
254	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
255	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
256	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
257	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
258	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
259	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
260	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
261	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
262	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
263	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
264	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
265	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
266	7901752	Discovery of a novel class of neuromedin B receptor antagonists, substituted somatostatin analogues.
267	7901752	Recent studies show two subtypes of receptors; a gastrin-releasing peptide (GRP) receptor subtype and a neuromedin B (NMB) receptor subtype exist.
268	7901752	In contrast to the GRP receptor, no antagonists exist for the NMB receptor.
269	7901752	In the present study we report that certain somatostatin (SS) octapeptide analogues function as selective NMB receptor antagonists.
270	7901752	The most potent analogue, D-Nal-Cys-Tyr-D-Trp-Lys-Val-Cys-Nal-NH2, inhibited binding of 125I-[D-Tyr degree]NMB to NMB receptor-transfected 3T3 cells and C6 cells.
271	7901752	The stereochemistry at positions 1, 2, 7, and 8, the hydrophobicity and ring size of the substitution in positions 1, 3, and 4, and the basicity of the group in position 5 were all important in determining NMB receptor affinity.
272	7901752	No SS octapeptide analogue increased [3H]inositol phosphates in NMB receptor-transfected cells; however, each analogue inhibited NMB-stimulated increases.
273	7901752	The results demonstrate for the first time a class of antagonists with > 100-fold selectivity for NMB versus GRP receptors.
274	7901752	Because the structural requirements for determining NMB, SS, and mu-opioid receptor activity differ, it is likely that highly selective, specific, high affinity NMB receptor antagonists can now be developed that will be useful in defining the role of NMB in various physiological processes.
275	7935330	Internalization of the gastrin-releasing peptide receptor is mediated by both phospholipase C-dependent and -independent processes.
276	7935330	Results with receptors linked to adenylate cyclase, such as the beta 2-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-dependent (i.e., protein kinase A or C) and -independent (i.e., beta-adrenergic receptor kinase) kinases in mediating this process.
277	7935330	Recent results for truncated and mutated gastrin-releasing peptide (GRP) receptors (GRP-R), as well as muscarinic cholinergic receptors, suggest that activation of protein kinase C may be needed for full receptor internalization.
278	7935330	We selectively mutated each of these residues in the GRP-R to determine their importance for activation of PLC.
279	7935330	Both R139G (Kd = 12.0 +/- 1.6 nM) and A263E (Kd = 12.2 +/- 1.7 nM) had a lower affinity for bombesin than did wild-type GRP-R (Kd = 1.4 +/- 0.4 nM); however, characteristic stoichiometries for the binding of agonists to this receptor were maintained equally in all three cell lines (bombesin > GRP >> neuromedin B).
280	7935330	The wild-type GRP-R exposed to bombesin increased [3H]inositol phosphates (a measure of PLC activation) approximately 4-fold, with an EC50 of 5.1 +/- 2.2 nM.
281	7935330	In contrast, [3H]inositol phosphates were not significantly increased in cells expressing R139G or A263E receptors, demonstrating that Arg139 and Ala263 are required for GRP-R activation of PLC.
282	7947701	In the present study, we investigated the nature and the importance of glycosylation of two mammalian bombesin receptors, the neuromedin B receptor (NMB-R) and the gastrin-releasing peptide receptor (GRP-R), using chemical cross-linking and enzymatic deglycosylation. [125I]-(D-Tyr0)NMB cross-linked to native NMB-R on rat C-6 glioblastoma cells or rat NMB-R transfected into BALB 3T3 cells revealed a single broad band, M(r) = 63,000, on both cell types that was not altered by DTT.
283	7947701	NMB inhibited cross-linking specifically and saturably with an IC50 of 4.8 and 6.1 nM for C-6 and NMB-R transfected cells, respectively, and there was a close correlation between its ability to inhibit binding and its ability to inhibit cross-linking.
284	7947701	A single broad band of M(r) = 82,000 was cross-linked with [125I]GRP on mouse GRP-R transfected BALB 3T3 cells.
285	7947701	Peptide-N4-(N-acetyl-beta- glucosaminyl)asparagine amidase F (PNGase F) digestion increased the mobility of the original band in C-6, NMB-R, and GRP-R transfected cell membranes.
286	7947701	Neuraminidase digestion slightly increased the mobility of the original band in NMB-R transfected cell membranes; however, it had no effect on GRP-R transfected cell membranes.
287	7947701	Endo-alpha-N-acetylglucosaminidase (O-glycanase) digestion subsequent to neuraminidase treatment showed no additional effect on either receptor.
288	7947701	Treatment of unlabeled membranes with PNGase F followed by affinity labeling resulted in fully deglycosylated NMB-R or 75% deglycosylated GRP-R.
289	7947701	Deglycosylation of the NMB-R did not alter its affinity for NMB or alter G-protein coupling; however, 75% deglycosylation of the GRP-R both decreased its affinity for GRP and altered its ability to couple to G-proteins.
290	7947701	In the present study, we investigated the nature and the importance of glycosylation of two mammalian bombesin receptors, the neuromedin B receptor (NMB-R) and the gastrin-releasing peptide receptor (GRP-R), using chemical cross-linking and enzymatic deglycosylation. [125I]-(D-Tyr0)NMB cross-linked to native NMB-R on rat C-6 glioblastoma cells or rat NMB-R transfected into BALB 3T3 cells revealed a single broad band, M(r) = 63,000, on both cell types that was not altered by DTT.
291	7947701	NMB inhibited cross-linking specifically and saturably with an IC50 of 4.8 and 6.1 nM for C-6 and NMB-R transfected cells, respectively, and there was a close correlation between its ability to inhibit binding and its ability to inhibit cross-linking.
292	7947701	A single broad band of M(r) = 82,000 was cross-linked with [125I]GRP on mouse GRP-R transfected BALB 3T3 cells.
293	7947701	Peptide-N4-(N-acetyl-beta- glucosaminyl)asparagine amidase F (PNGase F) digestion increased the mobility of the original band in C-6, NMB-R, and GRP-R transfected cell membranes.
294	7947701	Neuraminidase digestion slightly increased the mobility of the original band in NMB-R transfected cell membranes; however, it had no effect on GRP-R transfected cell membranes.
295	7947701	Endo-alpha-N-acetylglucosaminidase (O-glycanase) digestion subsequent to neuraminidase treatment showed no additional effect on either receptor.
296	7947701	Treatment of unlabeled membranes with PNGase F followed by affinity labeling resulted in fully deglycosylated NMB-R or 75% deglycosylated GRP-R.
297	7947701	Deglycosylation of the NMB-R did not alter its affinity for NMB or alter G-protein coupling; however, 75% deglycosylation of the GRP-R both decreased its affinity for GRP and altered its ability to couple to G-proteins.
298	7947701	In the present study, we investigated the nature and the importance of glycosylation of two mammalian bombesin receptors, the neuromedin B receptor (NMB-R) and the gastrin-releasing peptide receptor (GRP-R), using chemical cross-linking and enzymatic deglycosylation. [125I]-(D-Tyr0)NMB cross-linked to native NMB-R on rat C-6 glioblastoma cells or rat NMB-R transfected into BALB 3T3 cells revealed a single broad band, M(r) = 63,000, on both cell types that was not altered by DTT.
299	7947701	NMB inhibited cross-linking specifically and saturably with an IC50 of 4.8 and 6.1 nM for C-6 and NMB-R transfected cells, respectively, and there was a close correlation between its ability to inhibit binding and its ability to inhibit cross-linking.
300	7947701	A single broad band of M(r) = 82,000 was cross-linked with [125I]GRP on mouse GRP-R transfected BALB 3T3 cells.
301	7947701	Peptide-N4-(N-acetyl-beta- glucosaminyl)asparagine amidase F (PNGase F) digestion increased the mobility of the original band in C-6, NMB-R, and GRP-R transfected cell membranes.
302	7947701	Neuraminidase digestion slightly increased the mobility of the original band in NMB-R transfected cell membranes; however, it had no effect on GRP-R transfected cell membranes.
303	7947701	Endo-alpha-N-acetylglucosaminidase (O-glycanase) digestion subsequent to neuraminidase treatment showed no additional effect on either receptor.
304	7947701	Treatment of unlabeled membranes with PNGase F followed by affinity labeling resulted in fully deglycosylated NMB-R or 75% deglycosylated GRP-R.
305	7947701	Deglycosylation of the NMB-R did not alter its affinity for NMB or alter G-protein coupling; however, 75% deglycosylation of the GRP-R both decreased its affinity for GRP and altered its ability to couple to G-proteins.
306	8163469	Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization.
307	8163469	The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract.
308	8163469	While it is known that this receptor is coupled to phospholipase C, like many other phospholipase C-activating receptors, little is known about regulation of the NMB-R subsequent to agonist stimulation.
309	8163469	Both cell types rapidly increased [3H]inositol phosphates and [Ca2+]i in response to 1 microM NMB, whereas preincubation with 3 nM NMB for 3 h markedly attenuated the ability of 1 microM NMB, but not 1 microM endothelin-1, to alter either cell type's biological activity.
310	8163469	Prolonged exposure to 3 nM NMB caused a rapid decrease in the number of NMB-R, with the maximal receptor down-regulation seen at 24 h due to NMB-R internalization.
311	8163469	Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization.
312	8163469	The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract.
313	8163469	While it is known that this receptor is coupled to phospholipase C, like many other phospholipase C-activating receptors, little is known about regulation of the NMB-R subsequent to agonist stimulation.
314	8163469	Both cell types rapidly increased [3H]inositol phosphates and [Ca2+]i in response to 1 microM NMB, whereas preincubation with 3 nM NMB for 3 h markedly attenuated the ability of 1 microM NMB, but not 1 microM endothelin-1, to alter either cell type's biological activity.
315	8163469	Prolonged exposure to 3 nM NMB caused a rapid decrease in the number of NMB-R, with the maximal receptor down-regulation seen at 24 h due to NMB-R internalization.
316	8163469	Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization.
317	8163469	The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract.
318	8163469	While it is known that this receptor is coupled to phospholipase C, like many other phospholipase C-activating receptors, little is known about regulation of the NMB-R subsequent to agonist stimulation.
319	8163469	Both cell types rapidly increased [3H]inositol phosphates and [Ca2+]i in response to 1 microM NMB, whereas preincubation with 3 nM NMB for 3 h markedly attenuated the ability of 1 microM NMB, but not 1 microM endothelin-1, to alter either cell type's biological activity.
320	8163469	Prolonged exposure to 3 nM NMB caused a rapid decrease in the number of NMB-R, with the maximal receptor down-regulation seen at 24 h due to NMB-R internalization.
321	8163469	Desensitization of neuromedin B receptors (NMB-R) on native and NMB-R-transfected cells involves down-regulation and internalization.
322	8163469	The receptor for neuromedin B (NMB-R), a mammalian bombesin-related peptide, is widely distributed in the central nervous system and gastrointestinal tract.
323	8163469	While it is known that this receptor is coupled to phospholipase C, like many other phospholipase C-activating receptors, little is known about regulation of the NMB-R subsequent to agonist stimulation.
324	8163469	Both cell types rapidly increased [3H]inositol phosphates and [Ca2+]i in response to 1 microM NMB, whereas preincubation with 3 nM NMB for 3 h markedly attenuated the ability of 1 microM NMB, but not 1 microM endothelin-1, to alter either cell type's biological activity.
325	8163469	Prolonged exposure to 3 nM NMB caused a rapid decrease in the number of NMB-R, with the maximal receptor down-regulation seen at 24 h due to NMB-R internalization.
326	8380344	Recent cloning studies confirm two subtypes of Bn receptors exist, a neuromedin B-preferring receptor (NMB-R) and a gastrin-releasing peptide-preferring receptor (GRP-R).
327	8380344	Both subtypes occur widely in GI tract and the CNS; however, in contrast to the GRP-R subtype little is known about the ligand-receptor interactions for the NMB-R.
328	8380344	Therefore, in the present study we explored the ligand-receptor interactions including kinetics, stoichiometry, internalization, degradation and regulation by guanine nucleotide binding proteins with the NMB-R and compared it to the GRP-R.
329	8380344	The rat glioblastoma C-6 cell line which possess functional NMB-R and 3T3 cells which possess functional GRP-R were used. 125I-[D-Tyr0]NMB and 125I-[Tyr4]Bn were prepared using Iodogen and purified on HPLC.
330	8380344	At 37 degrees C binding of 125I-[D-Tyr0]NMB to NMB-R or 125I-[Tyr4]Bn to GRP-R was maximal by 5-15 min and decreased to 60-70% after 60 min.
331	8380344	These results demonstrated that NMB receptors, similar to GRP receptors and rapidly internalize bound agonists and rapidly degrade agonists.
332	8380344	Recent cloning studies confirm two subtypes of Bn receptors exist, a neuromedin B-preferring receptor (NMB-R) and a gastrin-releasing peptide-preferring receptor (GRP-R).
333	8380344	Both subtypes occur widely in GI tract and the CNS; however, in contrast to the GRP-R subtype little is known about the ligand-receptor interactions for the NMB-R.
334	8380344	Therefore, in the present study we explored the ligand-receptor interactions including kinetics, stoichiometry, internalization, degradation and regulation by guanine nucleotide binding proteins with the NMB-R and compared it to the GRP-R.
335	8380344	The rat glioblastoma C-6 cell line which possess functional NMB-R and 3T3 cells which possess functional GRP-R were used. 125I-[D-Tyr0]NMB and 125I-[Tyr4]Bn were prepared using Iodogen and purified on HPLC.
336	8380344	At 37 degrees C binding of 125I-[D-Tyr0]NMB to NMB-R or 125I-[Tyr4]Bn to GRP-R was maximal by 5-15 min and decreased to 60-70% after 60 min.
337	8380344	These results demonstrated that NMB receptors, similar to GRP receptors and rapidly internalize bound agonists and rapidly degrade agonists.
338	8380344	Recent cloning studies confirm two subtypes of Bn receptors exist, a neuromedin B-preferring receptor (NMB-R) and a gastrin-releasing peptide-preferring receptor (GRP-R).
339	8380344	Both subtypes occur widely in GI tract and the CNS; however, in contrast to the GRP-R subtype little is known about the ligand-receptor interactions for the NMB-R.
340	8380344	Therefore, in the present study we explored the ligand-receptor interactions including kinetics, stoichiometry, internalization, degradation and regulation by guanine nucleotide binding proteins with the NMB-R and compared it to the GRP-R.
341	8380344	The rat glioblastoma C-6 cell line which possess functional NMB-R and 3T3 cells which possess functional GRP-R were used. 125I-[D-Tyr0]NMB and 125I-[Tyr4]Bn were prepared using Iodogen and purified on HPLC.
342	8380344	At 37 degrees C binding of 125I-[D-Tyr0]NMB to NMB-R or 125I-[Tyr4]Bn to GRP-R was maximal by 5-15 min and decreased to 60-70% after 60 min.
343	8380344	These results demonstrated that NMB receptors, similar to GRP receptors and rapidly internalize bound agonists and rapidly degrade agonists.
344	8380344	Recent cloning studies confirm two subtypes of Bn receptors exist, a neuromedin B-preferring receptor (NMB-R) and a gastrin-releasing peptide-preferring receptor (GRP-R).
345	8380344	Both subtypes occur widely in GI tract and the CNS; however, in contrast to the GRP-R subtype little is known about the ligand-receptor interactions for the NMB-R.
346	8380344	Therefore, in the present study we explored the ligand-receptor interactions including kinetics, stoichiometry, internalization, degradation and regulation by guanine nucleotide binding proteins with the NMB-R and compared it to the GRP-R.
347	8380344	The rat glioblastoma C-6 cell line which possess functional NMB-R and 3T3 cells which possess functional GRP-R were used. 125I-[D-Tyr0]NMB and 125I-[Tyr4]Bn were prepared using Iodogen and purified on HPLC.
348	8380344	At 37 degrees C binding of 125I-[D-Tyr0]NMB to NMB-R or 125I-[Tyr4]Bn to GRP-R was maximal by 5-15 min and decreased to 60-70% after 60 min.
349	8380344	These results demonstrated that NMB receptors, similar to GRP receptors and rapidly internalize bound agonists and rapidly degrade agonists.
350	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
351	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
352	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
353	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
354	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
355	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
356	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
357	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
358	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
359	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
360	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
361	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
362	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
363	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
364	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
365	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
366	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
367	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
368	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
369	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
370	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
371	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
372	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
373	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
374	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
375	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
376	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
377	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
378	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
379	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
380	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
381	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
382	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
383	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
384	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
385	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
386	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
387	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
388	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
389	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
390	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
391	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
392	8788416	Recently it has been established that both a gastrin-releasing peptide (GRP)-preferring bombesin receptor and a neuromedin B-preferring bombesin receptor mediate the mammalian actions of bombesin-related peptides.
393	8788416	Because many tissues used for studies of the structure-activity relationship of these peptides possess both receptor subtypes and none possess only the neuromedin B-preferring subtype, there is minimal information on the peptide structural features determining receptor selectivity and it is unknown whether the determinants of agonism at both bombesin receptor subtypes are similar.
394	8788416	For the naturally occurring agonists, at the GRP-preferring bombesin receptor the relative affinities were litorin = ranatensin = bombesin > GRP >> neuromedin B, phyllolitorin and at the neuromedin B-preferring bombesin receptor were litorin = neuromedin B = ranatensin > bombesin, phyllolitorin >> GRP.
395	8788416	For the GRP-preferring bombesin receptor the heptapeptide and for the neuromedin B-preferring bombesin receptor the octapeptide was the minimal carboxyl fragment interacting with the receptor/or causing biologic activity, and the nonapeptide and full decapeptide, respectively, were the minimal required for full affinity.
396	8788416	Making neuromedin B more bombesin- or GRP-like by replacing amino acids in position 3, 6, and 9 demonstrated that position 3 was the most important, followed by position 9 for receptor subtype selectivity.
397	8788416	A conformationally restricted GRP analogue, [D-Cys6,D-Ala11,Cys14]bombesin-(6-14) had a significantly higher affinity for GRP-preferring bombesin receptor than NMB receptor.
398	8788416	These results demonstrate that: (1) the structure-function relations for the two mammalian bombesin receptors have important differences; (2) suggest that the active conformation of neuromedin B must differ markedly from the beta-sheet model proposed for GRP; and (3) suggest that one important function of the NH2 terminus of GRP and neuromedin B is determining receptor subtype selectivity.
399	9030820	Neuromedin B is a bombesin-like peptide highly concentrated in the pituitary gland that has been shown to have inhibitory action on TSH secretion, acting as an autocrine/paracrine factor.
400	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
401	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
402	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
403	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
404	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
405	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
406	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
407	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
408	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
409	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
410	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
411	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
412	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
413	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
414	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
415	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
416	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
417	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
418	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
419	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
420	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
421	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
422	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
423	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
424	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
425	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
426	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
427	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
428	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
429	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
430	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
431	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
432	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
433	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
434	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
435	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
436	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
437	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
438	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
439	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
440	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
441	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
442	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
443	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
444	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
445	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
446	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
447	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
448	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
449	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
450	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
451	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
452	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
453	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
454	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
455	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
456	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
457	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
458	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
459	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
460	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
461	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
462	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
463	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
464	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
465	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
466	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
467	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
468	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
469	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
470	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
471	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
472	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
473	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
474	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
475	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
476	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
477	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
478	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
479	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
480	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
481	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
482	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
483	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
484	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
485	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
486	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
487	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
488	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
489	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
490	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
491	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
492	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
493	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
494	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
495	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
496	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
497	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
498	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
499	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
500	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
501	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
502	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
503	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
504	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
505	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
506	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
507	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
508	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
509	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
510	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
511	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
512	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
513	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
514	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
515	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
516	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
517	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
518	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
519	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
520	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
521	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
522	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
523	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
524	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
525	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
526	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
527	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
528	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
529	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
530	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
531	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
532	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
533	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
534	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
535	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
536	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
537	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
538	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
539	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
540	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
541	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
542	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
543	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
544	9405068	Neuromedin B receptor activation causes tyrosine phosphorylation of p125FAK by a phospholipase C independent mechanism which requires p21rho and integrity of the actin cytoskeleton.
545	9405068	Neuromedin B (NMB), a mammalian bombesin related peptide, functions through a distinct receptor, the neuromedin B receptor (NMB-R), of which little is known about its cellular basis of action.
546	9405068	In the present study we explored the ability of NMB-R activation to cause tyrosine phosphorylation of focal adhesion kinase (p125(FAK)), an important substrate for tyrosine phosphorylation by other neuropeptides.
547	9405068	NMB caused rapid increases in p125(FAK) phosphorylation which reached maximum at 2 min in both rat C6 glioblastoma cells which possess native NMB-Rs and rat neuromedin B receptor (rNMR-R) transfected BALB 3T3 cells.
548	9405068	NMB had a half-maximal effect was at 0.4 nM and was 30-fold more potent than gastrin-releasing peptide (GRP).
549	9405068	The stoichiometric relationships between increased p125(FAK) tyrosine phosphorylation and other cellular processes was similar in both C6 cells and rNMB-R transfected cells.
550	9405068	TPA (1 microM) caused 45% and the calcium ionophore, A23187, 11% of maximal tyrosine phosphorylation of p125(FAK) seen with NMB.
551	9405068	Pretreatment with the selective PKC inhibitor, GF109203X, inhibited TPA-induced p125(FAK) tyrosine phosphorylation, but it had no effect on the NMB stimulation.
552	9405068	Pretreatment with thapsigargin completely inhibited NMB-stimulated increases in [Ca2+]i, but had no effect on NMB-stimulation of p125(FAK) phosphorylation either alone or with GF109203X.
553	9405068	The tyrosine kinase inhibitor, tyrphostin A25, inhibited NMB-induced phosphorylation of p125(FAK) by 52%.
554	9405068	Cytochalasin D, an agent which disrupts actin microfilaments, inhibited BN- and TPA-induced tyrosine phosphorylation of p125(FAK) completely.
555	9405068	Pretreatment with Clostridium botulinum C3 exoenzyme which inactivates the small GTP-binding protein rho p21, also inhibited tyrosine phosphorylation of p125(FAK) by 55%.
556	9405068	These results demonstrate that activation of NMB-R can cause rapid tyrosine phosphorylation of p125(FAK).
557	9405068	NMB-induced tyrosine phosphorylation of p125(FAK) is independent of NMB-induced changes in [Ca2+]i or PKC.
558	9405068	The integrity of the actin cytoskeleton but not of microtubules is necessary for NMB-stimulated phosphorylation of p125(FAK).
559	9405068	The ras-related small GTP-binding protein rho p21 is at least partially involved in mediating NMB-induced tyrosine phosphorylation of p125(FAK).
560	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
561	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
562	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
563	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
564	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
565	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
566	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
567	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
568	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
569	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
570	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
571	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
572	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
573	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
574	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
575	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
576	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
577	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
578	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
579	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
580	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
581	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
582	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
583	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
584	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
585	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
586	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
587	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
588	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
589	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
590	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
591	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
592	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
593	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
594	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
595	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
596	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
597	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
598	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
599	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
600	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
601	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
602	9555086	Neuromedin B activates phospholipase D through both PKC-dependent and PKC-independent mechanisms.
603	9555086	The actions of neuromedin B (NMB), a recently discovered mammalian bombesin-related peptide, are mediated by interacting with a distinct receptor; however, little is known about its cellular basis of action.
604	9555086	The purpose of the present study was to determine whether activation of the NMB receptor causes activation of PLD and to explore whether this activation was coupled to PLC activation.
605	9555086	Increases in PLD activity were rapid and NMB was 100-fold more potent than gastrin-releasing peptide (GRP).
606	9555086	The Ca2+-ATPase inhibitor, thapsigargin, did not affect NMB- or TPA-stimulated PLD activities, although it blocked completely the NMB-induced increase in [Ca2+]i.
607	9555086	These data indicate that NMB receptor activation is coupled to both PLC and PLD.
608	9555086	In contrast to a number of other phospholipase C-coupled receptors, NMB receptor stimulated changes in [Ca2+]i do not contribute to PLD activation.
609	9593699	Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3.
610	9593699	Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a predicted member of the heptahelical G-protein receptor family and so named because it shares a 50% amino acid homology with receptors for the mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide.
611	9593699	[D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2-3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in cyclic AMP or inhibit forskolin-stimulated increases.
612	9593699	No high affinity Bn receptor antagonists had high affinity for the hBRS-3 receptor, although two low affinity antagonists for gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation.
613	9593699	The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2 inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM).
614	9593699	Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination.
615	9593699	These results show that hBRS-3 receptor activation increases phospholipase C activity, which causes generation of inositol phosphates and changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation results in tyrosine phosphorylation of p125(FAK), and it is not dependent on activation of either limb of the phospholipase C cascade.
616	9593699	Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3.
617	9593699	Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a predicted member of the heptahelical G-protein receptor family and so named because it shares a 50% amino acid homology with receptors for the mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide.
618	9593699	[D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2-3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in cyclic AMP or inhibit forskolin-stimulated increases.
619	9593699	No high affinity Bn receptor antagonists had high affinity for the hBRS-3 receptor, although two low affinity antagonists for gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation.
620	9593699	The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2 inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM).
621	9593699	Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination.
622	9593699	These results show that hBRS-3 receptor activation increases phospholipase C activity, which causes generation of inositol phosphates and changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation results in tyrosine phosphorylation of p125(FAK), and it is not dependent on activation of either limb of the phospholipase C cascade.
623	9593699	Ability of various bombesin receptor agonists and antagonists to alter intracellular signaling of the human orphan receptor BRS-3.
624	9593699	Bombesin (Bn) receptor subtype 3 (BRS-3) is an orphan receptor that is a predicted member of the heptahelical G-protein receptor family and so named because it shares a 50% amino acid homology with receptors for the mammalian bombesin-like peptides neuromedin B (NMB) and gastrin-releasing peptide.
625	9593699	[D-Phe6,beta-Ala11,Phe13,Nle14]Bn-(6-14) stimulated a 2-3-fold increase in [Ca2+]i, a 3-fold increase in tyrosine phosphorylation of p125(FAK) with an EC50 of 0.2-0.7 nM, but failed to either stimulate increases in cyclic AMP or inhibit forskolin-stimulated increases.
626	9593699	No high affinity Bn receptor antagonists had high affinity for the hBRS-3 receptor, although two low affinity antagonists for gastrin-releasing peptide and NMB receptors, [D-Arg1,D-Trp7,9, Leu11]substance P and [D-Pro4,D-Trp7,9,10]substance P-(4-11), inhibited hBRS-3 receptor activation.
627	9593699	The NMB receptor-specific antagonist D-Nal,Cys,Tyr,D-Trp,Lys,Val, Cys,Nal-NH2 inhibited hBRS-3 receptor activation in a competitive fashion (Ki = 0.5 microM).
628	9593699	Stimulation of p125(FAK) tyrosine phosphorylation by hBRS-3 activation was not inhibited by the protein kinase C inhibitor, GF109203X, or thapsigargin, alone or in combination.
629	9593699	These results show that hBRS-3 receptor activation increases phospholipase C activity, which causes generation of inositol phosphates and changes in [Ca2+]i and is also coupled to tyrosine kinase activation, but is not coupled to adenylate cyclase activation or inhibition. hBRS-3 receptor activation results in tyrosine phosphorylation of p125(FAK), and it is not dependent on activation of either limb of the phospholipase C cascade.
630	10454496	Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist.
631	10454496	Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog.
632	10454496	In binding studies, PD 168368 had similar high affinities (K(i) = 15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4.
633	10454496	PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
634	10454496	Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist.
635	10454496	Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog.
636	10454496	In binding studies, PD 168368 had similar high affinities (K(i) = 15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4.
637	10454496	PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
638	10454496	Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist.
639	10454496	Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog.
640	10454496	In binding studies, PD 168368 had similar high affinities (K(i) = 15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4.
641	10454496	PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
642	10454496	Recently, the peptoid PD 168368 was found to be a potent human NMB receptor antagonist.
643	10454496	Because it had been shown previously that either synthetic analogs of bombesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor subtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor subtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor subtype 3, and Bn receptor subtype 4) from human, mouse, rat, and frog.
644	10454496	In binding studies, PD 168368 had similar high affinities (K(i) = 15-45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor subtype 3 or 4.
645	10454496	PD 168368 should prove useful for delineating the biological role of NMB and selectively blocking NMB signaling in bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
646	12021405	Molecular basis of the selectivity of gastrin-releasing peptide receptor for gastrin-releasing peptide.
647	12021405	The mammalian bombesin peptides [gastrin-releasing peptide (GRP) and neuromedin B (NMB)] are important in numerous biological and pathological processes.
648	12021405	These effects are mediated by the heptahelical GRP receptor (GRPR) and NMB receptor (NMBR).
649	12021405	GRP has high affinity for GRPR and lower affinity for NMBR.
650	12021405	To address this question, we first studied four loss-of-affinity GRPR chimeric receptors formed by exchanging the four extracellular (EC) domains of GRPR with the corresponding NMBR EC domains.
651	12021405	Only substitution of the third EC domain (EC3) of GRPR markedly decreased GRP affinity.
652	12021405	In the reverse study using gain-of-affinity NMBR chimeras, only replacement of EC3 of NMBR markedly increased GRP affinity.
653	12021405	Replacing each of the 20 comparable EC3 amino acids that differed in the NMBR in GRPR showed that two separate NMBR substitutions in the GRPR, Ile for Phe(185) or Ile for Ala(198), markedly decreased GRP affinity.
654	12021405	Additional point mutants demonstrated that an amino acid with an aromatic ring in position 185 of GRPR and the size of the backbone substitution in position 198 of GRPR were important for GRP selectivity.
655	12021405	These results demonstrate that selectivity of GRP for GRPR over NMBR is primarily determined by two amino acid differences in the EC3 domains of the receptor.
656	12021405	Our results suggest that an interaction between the aromatic ring of Phe(185) of the GRPR with GRP is the most important for GRP selectivity.
657	12021405	Molecular basis of the selectivity of gastrin-releasing peptide receptor for gastrin-releasing peptide.
658	12021405	The mammalian bombesin peptides [gastrin-releasing peptide (GRP) and neuromedin B (NMB)] are important in numerous biological and pathological processes.
659	12021405	These effects are mediated by the heptahelical GRP receptor (GRPR) and NMB receptor (NMBR).
660	12021405	GRP has high affinity for GRPR and lower affinity for NMBR.
661	12021405	To address this question, we first studied four loss-of-affinity GRPR chimeric receptors formed by exchanging the four extracellular (EC) domains of GRPR with the corresponding NMBR EC domains.
662	12021405	Only substitution of the third EC domain (EC3) of GRPR markedly decreased GRP affinity.
663	12021405	In the reverse study using gain-of-affinity NMBR chimeras, only replacement of EC3 of NMBR markedly increased GRP affinity.
664	12021405	Replacing each of the 20 comparable EC3 amino acids that differed in the NMBR in GRPR showed that two separate NMBR substitutions in the GRPR, Ile for Phe(185) or Ile for Ala(198), markedly decreased GRP affinity.
665	12021405	Additional point mutants demonstrated that an amino acid with an aromatic ring in position 185 of GRPR and the size of the backbone substitution in position 198 of GRPR were important for GRP selectivity.
666	12021405	These results demonstrate that selectivity of GRP for GRPR over NMBR is primarily determined by two amino acid differences in the EC3 domains of the receptor.
667	12021405	Our results suggest that an interaction between the aromatic ring of Phe(185) of the GRPR with GRP is the most important for GRP selectivity.
668	15102928	The human bombesin receptor subtype 3 (hBRS-3) orphan receptor, which has a high homology to bombesin (Bn) receptors [gastrin-releasing peptide (GRP) and neuromedin B (NMB) receptors], is widely distributed in the rat central nervous system.
669	15670577	Identification of key amino acids in the gastrin-releasing peptide receptor (GRPR) responsible for high affinity binding of gastrin-releasing peptide (GRP).
670	15670577	The bombesin (Bn) receptor family includes the gastrin-releasing peptide (GRPR) and neuromedin B (NMBR) receptors, Bn receptor subtype 3 (BRS-3) and Bn receptor subtype 4 (BB(4)).
671	15670577	They share 50% homology, yet their affinities for gastrin-releasing peptide (GRP) differ.
672	15670577	The determinants of GRP high affinity for GRPR and BB(4), and low affinity for BRS-3 are largely unknown.
673	15670577	Furthermore, three of four amino acids in the GRPR selected used a similar approach and previously reported to be important for high affinity Bn binding, were important for GRP affinity.
674	15670577	Some GRPR mutants containing combinations of these mutations had greater decreases in GRP affinity than any single mutation.
675	15670577	Particularly important for GRP selectivity were K101, Q121, A198, P199, S293, R288, T297 in GRPR.
676	18055507	The mammalian bombesin receptor family comprises three G protein-coupled heptahelical receptors: the neuromedin B (NMB) receptor (BB(1)), the gastrin-releasing peptide (GRP) receptor (BB(2)), and the orphan receptor bombesin receptor subtype 3 (BRS-3) (BB(3)).
677	18055507	The mammalian bombesin peptides, GRP and NMB, demonstrate a broad spectrum of pharmacological/biological responses.
678	18055507	NMB causes contraction of smooth muscle, has growth effects in various tissues, has CNS effects, including effects on feeding and thermoregulation, regulates thyroid-stimulating hormone release, stimulates various CNS neurons, has behavioral effects, and has effects on spinal sensory transmission.
679	18055507	GRP, and to a lesser extent NMB, affects growth and/or differentiation of various human tumors, including colon, prostate, lung, and some gynecologic cancers.
680	18055507	The mammalian bombesin receptor family comprises three G protein-coupled heptahelical receptors: the neuromedin B (NMB) receptor (BB(1)), the gastrin-releasing peptide (GRP) receptor (BB(2)), and the orphan receptor bombesin receptor subtype 3 (BRS-3) (BB(3)).
681	18055507	The mammalian bombesin peptides, GRP and NMB, demonstrate a broad spectrum of pharmacological/biological responses.
682	18055507	NMB causes contraction of smooth muscle, has growth effects in various tissues, has CNS effects, including effects on feeding and thermoregulation, regulates thyroid-stimulating hormone release, stimulates various CNS neurons, has behavioral effects, and has effects on spinal sensory transmission.
683	18055507	GRP, and to a lesser extent NMB, affects growth and/or differentiation of various human tumors, including colon, prostate, lung, and some gynecologic cancers.
684	18055507	The mammalian bombesin receptor family comprises three G protein-coupled heptahelical receptors: the neuromedin B (NMB) receptor (BB(1)), the gastrin-releasing peptide (GRP) receptor (BB(2)), and the orphan receptor bombesin receptor subtype 3 (BRS-3) (BB(3)).
685	18055507	The mammalian bombesin peptides, GRP and NMB, demonstrate a broad spectrum of pharmacological/biological responses.
686	18055507	NMB causes contraction of smooth muscle, has growth effects in various tissues, has CNS effects, including effects on feeding and thermoregulation, regulates thyroid-stimulating hormone release, stimulates various CNS neurons, has behavioral effects, and has effects on spinal sensory transmission.
687	18055507	GRP, and to a lesser extent NMB, affects growth and/or differentiation of various human tumors, including colon, prostate, lung, and some gynecologic cancers.
688	18055507	The mammalian bombesin receptor family comprises three G protein-coupled heptahelical receptors: the neuromedin B (NMB) receptor (BB(1)), the gastrin-releasing peptide (GRP) receptor (BB(2)), and the orphan receptor bombesin receptor subtype 3 (BRS-3) (BB(3)).
689	18055507	The mammalian bombesin peptides, GRP and NMB, demonstrate a broad spectrum of pharmacological/biological responses.
690	18055507	NMB causes contraction of smooth muscle, has growth effects in various tissues, has CNS effects, including effects on feeding and thermoregulation, regulates thyroid-stimulating hormone release, stimulates various CNS neurons, has behavioral effects, and has effects on spinal sensory transmission.
691	18055507	GRP, and to a lesser extent NMB, affects growth and/or differentiation of various human tumors, including colon, prostate, lung, and some gynecologic cancers.