Ignet

Gene Information

Gene symbol: CYSLTR2

Gene name: cysteinyl leukotriene receptor 2

HGNC ID: 18274

Synonyms: CysLT(2), CYSLT2R

Related Genes

#	Gene Symbol	Number of hits
1	ADCY1	1 hits
2	ADRB2	1 hits
3	AGT	1 hits
4	ASPM	1 hits
5	CASR	1 hits
6	CHRNA9	1 hits
7	CNO	1 hits
8	CRY1	1 hits
9	CXCR4	1 hits
10	CYSLTR1	1 hits
11	EGF	1 hits
12	EGFR	1 hits
13	FFAR1	1 hits
14	FFAR2	1 hits
15	FFAR3	1 hits
16	GCG	1 hits
17	GIP	1 hits
18	GIPR	1 hits
19	GLP1R	1 hits
20	GNAS	1 hits
21	GNAT1	1 hits
22	GPR109A	1 hits
23	GPR119	1 hits
24	GPR120	1 hits
25	GPR21	1 hits
26	GPR35	1 hits
27	GPR84	1 hits
28	GPRC5C	1 hits
29	GRK5	1 hits
30	INDO	1 hits
31	INHBE	1 hits
32	INS	1 hits
33	INSR	1 hits
34	NTS	1 hits
35	P2RY1	1 hits
36	P2RY12	1 hits
37	P2RY6	1 hits
38	PDGFB	1 hits
39	PDGFRA	1 hits
40	PDGFRB	1 hits
41	PGD	1 hits
42	PPARA	1 hits
43	PTGDS	1 hits
44	PTGER2	1 hits
45	PTGER4	1 hits
46	REEP5	1 hits
47	RGS16	1 hits
48	RGS8	1 hits
49	SRC	1 hits
50	SUCNR1	1 hits
51	TGFB1	1 hits

Related Sentences

#	PMID	Sentence
1	11701461	In this study, we demonstrated that CysLTs contribute to the contraction elicited by Ang II in isolated aortas from streptozotocin-induced diabetic (SS) rats but not from insulin-treated diabetic rats, fructose-fed rats, or control rats.
2	11701461	In contrast, the CysLT(1) receptor antagonist (MK571, 1 micromol/L) or the dual CysLT(1)/CysLT(2) receptor antagonist (BAY-u9773, 0.1 micromol/L) did not affect Ang II-induced contraction.
3	11701461	These data suggest the activation of the 5-lipoxygenase pathway in SS rats and the involvement of 5-lipoxygenase-derived products, particularly the CysLTs, in Ang II-induced contraction in aortas from SS rats through stimulation of CysLT receptors different from the well-characterized CysLT(1) or CysLT(2) receptor.
4	12502502	Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor.
5	12502502	We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol (PI) 3-kinase- and protein kinase C zeta-dependent manner.
6	12502502	However, the exact mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to promote beta-cell growth remains unknown.
7	12502502	We hypothesized that the GLP-1R could activate PI 3-kinase and promote beta-cell proliferation through transactivation of the epidermal growth factor (EGF) receptor (EGFR), an event possibly linked to GPCRs via activation of c-Src and the production of putative endogenous EGF-like ligands.
8	12502502	Both the c-Src inhibitor PP1 and the EGFR-specific inhibitor AG1478 blocked GLP-1-induced [(3)H]thymidine incorporation in INS(832/13) cells as well as in isolated rat islets, while only AG1478 inhibited the proliferative action of betacellulin (BTC), an EGFR agonist.
9	12502502	A time-dependent increase in tyrosine phosphorylation of the EGFR in response to GLP-1 was observed in INS(832/13) cells.
10	12502502	This transactivation of the EGFR was sensitive to both the pharmacological agents PP1 and AG1478.
11	12502502	The action of GLP-1 and BTC on INS cell proliferation was found to be not additive.
12	12502502	GLP-1 treatment of INS cells caused a decrease in cell surface-associated BTC, as shown by FACS analysis.
13	12502502	The results are consistent with a model in which GLP-1 increases PI 3-kinase activity and enhances beta-cell proliferation via transactivation of the EGFR that would require the proteolytic processing of membrane-anchored BTC or other EGF-like ligands.
14	12502502	Glucagon-like peptide 1 induces pancreatic beta-cell proliferation via transactivation of the epidermal growth factor receptor.
15	12502502	We previously provided evidence that glucagon-like peptide 1 (GLP-1) induces pancreatic beta-cell growth nonadditively with glucose in a phosphatidylinositol (PI) 3-kinase- and protein kinase C zeta-dependent manner.
16	12502502	However, the exact mechanism by which the GLP-1 receptor (GLP-1R), a member of the G protein-coupled receptor (GPCR) superfamily, activates the PI 3-kinase signaling pathway to promote beta-cell growth remains unknown.
17	12502502	We hypothesized that the GLP-1R could activate PI 3-kinase and promote beta-cell proliferation through transactivation of the epidermal growth factor (EGF) receptor (EGFR), an event possibly linked to GPCRs via activation of c-Src and the production of putative endogenous EGF-like ligands.
18	12502502	Both the c-Src inhibitor PP1 and the EGFR-specific inhibitor AG1478 blocked GLP-1-induced [(3)H]thymidine incorporation in INS(832/13) cells as well as in isolated rat islets, while only AG1478 inhibited the proliferative action of betacellulin (BTC), an EGFR agonist.
19	12502502	A time-dependent increase in tyrosine phosphorylation of the EGFR in response to GLP-1 was observed in INS(832/13) cells.
20	12502502	This transactivation of the EGFR was sensitive to both the pharmacological agents PP1 and AG1478.
21	12502502	The action of GLP-1 and BTC on INS cell proliferation was found to be not additive.
22	12502502	GLP-1 treatment of INS cells caused a decrease in cell surface-associated BTC, as shown by FACS analysis.
23	12502502	The results are consistent with a model in which GLP-1 increases PI 3-kinase activity and enhances beta-cell proliferation via transactivation of the EGFR that would require the proteolytic processing of membrane-anchored BTC or other EGF-like ligands.
24	15141213	Here we show that GPR91 (ref. 3), a previously orphan G-protein-coupled receptor (GPCR), functions as a receptor for the citric acid cycle intermediate succinate.
25	15141213	We also report that GPR99 (ref. 4), a close relative of GPR91, responds to alpha-ketoglutarate, another intermediate in the citric acid cycle.
26	15141213	The succinate-induced hypertensive effect involves the renin-angiotensin system and is abolished in GPR91-deficient mice.
27	15336602	Calcium-sensing receptor activation stimulates parathyroid hormone-related protein secretion in prostate cancer cells: role of epidermal growth factor receptor transactivation.
28	15336602	We have previously reported that high extracellular Ca2+ stimulates parathyroid hormone-related protein (PTHrP) release from human prostate and breast cancer cell lines as well as from H-500 rat Leydig cancer cells, an action mediated by the calcium-sensing receptor (CaR).
29	15336602	Activating the CaR leads to phosphorylation of mitogen-activated protein kinases (MAPKs) that participate in PTHrP synthesis and secretion.
30	15336602	Because the CaR is a G protein-coupled receptor (GPCR), it is likely to transactivate the epidermal growth factor receptor (EGFR) or the platelet-derived growth factor receptor (PDGFR).
31	15336602	In this study, we hypothesized that activation of the CaR transactivates the EGFR or PDGFR, and examined whether transactivation affects PTHrP secretion in PC-3 human prostate cancer cells.
32	15336602	Using Western analysis, we observed that an increase in extracellular Ca2+ resulted in delayed activation of extracellular signal-regulated kinase (ERK) in PC-3 cells.
33	15336602	Pre-incubation with AG1478 (an EGFR kinase inhibitor) or an EGFR neutralizing antibody inhibited the high Ca2+ -induced phosphorylation of ERK1/2.
34	15336602	GM6001, a pan matrix metalloproteinase (MMP) inhibitor, also partially suppressed the ERK activation, but AG1296 (a PDGFR kinase inhibitor) did not.
35	15336602	When cells were preincubated with AG1478, GM6001, or an antihuman heparin-binding EGF (HB-EGF) antibody, PTHrP secretion was significantly inhibited under basal as well as high Ca2+ conditions, while AG1296 had no effect on PTHrP secretion.
36	15336602	Taken together, these findings indicate that activation of the CaR transactivates the EGFR, but not the PDGFR, leading to phosphorylation of ERK1/2 and resultant PTHrP secretion, although CaR-EGFR-ERK might not be the only signaling pathway for PTHrP secretion.
37	15336602	This transactivation is most likely mediated by activation of MMP and cleavage of proheparin-binding EGF (proHB-EGF) to HB-EGF.
38	17206152	Here we describe a new experimental strategy that allows rapid identification of functionally critical amino acids in the rat M(3) muscarinic acetylcholine receptor (M3R), a prototypic class I GPCR.
39	17306374	Its particular effects on insulin and glucagon secretion have generated a flurry of research activity over the past 20 years culminating in a naturally occurring GLP-1 receptor (GLP-1R) agonist, exendin 4 (Ex-4), now being used to treat type 2 diabetes mellitus (T2DM).
40	17306374	GLP-1 engages a specific guanine nucleotide-binding protein (G-protein) coupled receptor (GPCR) that is present in tissues other than the pancreas (brain, kidney, lung, heart, and major blood vessels).
41	17306374	The most widely studied cell activated by GLP-1 is the insulin-secreting beta cell where its defining action is augmentation of glucose-induced insulin secretion.
42	17306374	Upon GLP-1R activation, adenylyl cyclase (AC) is activated and cAMP is generated, leading, in turn, to cAMP-dependent activation of second messenger pathways, such as the protein kinase A (PKA) and Epac pathways.
43	17306374	As well as short-term effects of enhancing glucose-induced insulin secretion, continuous GLP-1R activation also increases insulin synthesis, beta cell proliferation, and neogenesis.
44	17430113	Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells.
45	17430113	The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2.
46	17430113	Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD.
47	17430113	Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2).
48	17430113	Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2).
49	17430113	These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively.
50	17430113	Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
51	17430113	Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells.
52	17430113	The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2.
53	17430113	Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD.
54	17430113	Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2).
55	17430113	Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2).
56	17430113	These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively.
57	17430113	Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
58	17437246	Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion.
59	17437246	We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR).
60	17437246	GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break.
61	17437246	A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template.
62	17437246	The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR.
63	17437246	On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex.
64	17437246	This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR.
65	17437246	Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion.
66	17437246	We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR).
67	17437246	GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break.
68	17437246	A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template.
69	17437246	The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR.
70	17437246	On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex.
71	17437246	This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR.
72	17437246	Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion.
73	17437246	We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR).
74	17437246	GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break.
75	17437246	A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template.
76	17437246	The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR.
77	17437246	On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex.
78	17437246	This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR.
79	17437246	Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced insulin secretion.
80	17437246	We have studied the structure of GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR).
81	17437246	GIP(1-30)NH2 has all the structural features of peptides belonging to family B1 GPCRs, which are characterized by a coil at the N-terminal and a long C-terminal alpha-helix with or without a break.
82	17437246	A model of the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on the principles of comparative protein modeling, using the crystal structure of bovine rhodopsin as a template.
83	17437246	The N-terminal domain of GIPR has been constructed from the NMR structure of the N-terminal of corticoptropin releasing factor receptor (CRFR), a family B1 GCPR.
84	17437246	On the basis of the experimental data available for some members of family B1 GPCRs, four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex.
85	17437246	This work is the first complete model at the atomic level of GIP(1-30)NH2 and of the complex with its GPCR.
86	18698756	Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119.
87	18698756	GPR119 is a rhodopsin-like GPCR expressed in pancreatic beta-cells and incretin releasing cells in the GI tract.
88	18838178	Several recent disulfide cross-linking studies using the M(3) muscarinic acetylcholine receptor as a model system have led to novel insights into the conformational changes associated with the activation of this prototypical class I GPCR.
89	19569204	In this study, we evaluated the applicability of ligand-based and structure-based models to quantitative affinity predictions and virtual screenings for ligands of the beta(2)-adrenergic receptor, a G protein-coupled receptor (GPCR).
90	19672815	Glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and G protein-coupled receptor 40 (GPR40) are members of G protein-coupled receptors (GPCR) family.
91	19672815	The expressions of GLP-1R, GIPR, GPR40, and a nuclear transcription factor - peroxisome-proliferator activated receptor alpha (PPARalpha) - were analyzed by real-time RT-PCR and immunoblotting.
92	19672815	We demonstrated that the expressions of GLP-1R, GIPR, and PPARalpha were downregulated when INS-1beta cells were treated with glucose, while their expressions were upregulated when treated with metformin or AICAR.
93	19672815	These results indicate that glucose, metformin, and AICAR regulated the expressions of incretin receptors and PPARalpha, but not GPR40 in beta cells.
94	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
95	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
96	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
97	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
98	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
99	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
100	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
101	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
102	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
103	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
104	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
105	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
106	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
107	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
108	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
109	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
110	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
111	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
112	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
113	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
114	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
115	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
116	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
117	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
118	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
119	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
120	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
121	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
122	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
123	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
124	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
125	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
126	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
127	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
128	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
129	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
130	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
131	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
132	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
133	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
134	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
135	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
136	19679549	Recently, we identified a novel crosstalk between insulin and G protein-coupled receptor (GPCR) signaling pathways in human pancreatic cancer cells.
137	19679549	Insulin enhanced GPCR signaling through a rapamycin-sensitive mTOR-dependent pathway.
138	19679549	Here, we determined whether metformin disrupts the crosstalk between insulin receptor and GPCR signaling in pancreatic cancer cells.
139	19679549	Treatment of human pancreatic cancer cells (PANC-1, MIAPaCa-2, and BxPC-3) with insulin (10 ng/mL) for 5 minutes markedly enhanced the increase in intracellular [Ca(2+)] induced by GPCR agonists (e.g., neurotensin, bradykinin, and angiotensin II).
140	19679549	Metformin pretreatment completely abrogated insulin-induced potentiation of Ca(2+) signaling but did not interfere with the effect of GPCR agonists alone.
141	19679549	Insulin also enhanced GPCR agonist-induced growth, measured by DNA synthesis, and the number of cells cultured in adherent or nonadherent conditions.
142	19679549	Low doses of metformin (0.1-0.5 mmol/L) blocked the stimulation of DNA synthesis, and the anchorage-dependent and anchorage-independent growth induced by insulin and GPCR agonists.
143	20446735	The P2Y(6) receptor is a cytoprotective G-protein-coupled receptor (GPCR) activated by UDP (EC(50) = 0.30 microM).
144	20446735	The conformationally constrained (S)-methanocarba-UDP is a full agonist (EC(50) = 0.042 microM). 4-Methoxyimino modification of pyrimidine enhanced P2Y(6), preserved P2Y(2) and P2Y(4), and abolished P2Y(14) receptor potency, in the appropriate nucleotide.
145	20565071	The P2Y(1) receptor is a prothrombotic G protein-coupled receptor (GPCR) activated by ADP.
146	20571025	Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor.
147	20571025	One component of classical G-protein-coupled receptor (GPCR) signaling invokes transactivation of protein tyrosine kinase receptors such as the epidermal growth factor receptor.
148	20571025	We have used the model of proteoglycan synthesis to demonstrate that the signaling paradigm of GPCR signaling can be extended to include the transactivation of serine/threonine receptor, specifically the TGF-beta type I receptor (TbetaRI) also known as activin-like kinase (ALK) V.
149	20571025	Thrombin stimulated elongation of GAG chains and increased proteoglycan core protein expression and these responses were blocked by the TbetaRI antagonist, SB431542 and TbetaRI siRNA knockdown, as well as several protease-activated receptor (PAR)-1 antagonists.
150	20571025	The canonical downstream response to TGF-beta is increased C-terminal phosphorylation of the transcription factor Smad2 generating phospho-Smad2C (phosphorylation of Smad2 C-terminal region).
151	20571025	The proteolytically inactive thrombin mimetic thrombin-receptor activating peptide also stimulated an increase in cytosolic phospho-Smad2C.
152	20571025	Thrombin stimulation of proteoglycan synthesis in vascular smooth muscle is mediated by protease-activated receptor-1 transactivation of the transforming growth factor beta type I receptor.
153	20571025	One component of classical G-protein-coupled receptor (GPCR) signaling invokes transactivation of protein tyrosine kinase receptors such as the epidermal growth factor receptor.
154	20571025	We have used the model of proteoglycan synthesis to demonstrate that the signaling paradigm of GPCR signaling can be extended to include the transactivation of serine/threonine receptor, specifically the TGF-beta type I receptor (TbetaRI) also known as activin-like kinase (ALK) V.
155	20571025	Thrombin stimulated elongation of GAG chains and increased proteoglycan core protein expression and these responses were blocked by the TbetaRI antagonist, SB431542 and TbetaRI siRNA knockdown, as well as several protease-activated receptor (PAR)-1 antagonists.
156	20571025	The canonical downstream response to TGF-beta is increased C-terminal phosphorylation of the transcription factor Smad2 generating phospho-Smad2C (phosphorylation of Smad2 C-terminal region).
157	20571025	The proteolytically inactive thrombin mimetic thrombin-receptor activating peptide also stimulated an increase in cytosolic phospho-Smad2C.
158	20616094	Rgs16 and Rgs8 in embryonic endocrine pancreas and mouse models of diabetes.
159	20616094	Here, we show that the regulators of G protein signaling Rgs16 and Rgs8 are expressed in pancreatic progenitor and endocrine cells during development, then extinguished in adults, but reactivated in models of both type 1 and type 2 diabetes.
160	20616094	Exendin-4, a glucagon-like peptide 1 (Glp-1)/incretin mimetic that stimulates beta-cell expansion, insulin secretion and normalization of blood glucose levels in diabetics, also promoted re-expression of Rgs16::GFP within a few days in pancreatic ductal-associated cells and islet beta-cells.
161	20616094	These findings show that Rgs16::GFP and Rgs8::GFP are novel and early reporters of G protein-coupled receptor (GPCR)-stimulated beta-cell expansion after therapeutic treatment and in diabetes models.
162	20616094	Rgs16 and Rgs8 are likely to control aspects of islet progenitor cell activation, differentiation and beta-cell expansion in embryos and metabolically stressed adults.
163	20852621	Elevations in circulating glucagon and epinephrine, two hormones that activate hepatic gluconeogenesis, trigger the cAMP-mediated phosphorylation of cAMP response element-binding protein (Creb) and dephosphorylation of the Creb-regulated transcription coactivator-2 (Crtc2)--two key transcriptional regulators of this process.
164	20852621	Circadian control of gene expression is achieved by two transcriptional activators, Clock and Bmal1, which stimulate cryptochrome (Cry1 and Cry2) and Period (Per1, Per2 and Per3) repressors that feed back on Clock-Bmal1 activity.
165	20852621	Here we show that Creb activity during fasting is modulated by Cry1 and Cry2, which are rhythmically expressed in the liver.
166	20852621	Cry1 expression was elevated during the night-day transition, when it reduced fasting gluconeogenic gene expression by blocking glucagon-mediated increases in intracellular cAMP concentrations and in the protein kinase A-mediated phosphorylation of Creb.
167	20852621	In biochemical reconstitution studies, we found that Cry1 inhibited accumulation of cAMP in response to G protein-coupled receptor (GPCR) activation but not to forskolin, a direct activator of adenyl cyclase.
168	20852621	As hepatic overexpression of Cry1 lowered blood glucose concentrations and improved insulin sensitivity in insulin-resistant db/db mice, our results suggest that compounds that enhance cryptochrome activity may provide therapeutic benefit to individuals with type 2 diabetes.
169	21392828	GPR35 is a poorly characterized G protein-coupled receptor (GPCR) that has been suggested as a potential therapeutic target for the treatment of diabetes, hypertension and asthma.
170	21461952	Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor.
171	21461952	The P2Y(12) receptor (P2Y(12)R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs.
172	21461952	Three homology models of P2Y(12)R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A(2A) adenosine receptor (A(2A)AR), and human C-X-C chemokine receptor type 4 (CXCR4).
173	21461952	Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor.
174	21461952	The P2Y(12) receptor (P2Y(12)R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs.
175	21461952	Three homology models of P2Y(12)R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A(2A) adenosine receptor (A(2A)AR), and human C-X-C chemokine receptor type 4 (CXCR4).
176	21461952	Comparison of three GPCR structural templates for modeling of the P2Y12 nucleotide receptor.
177	21461952	The P2Y(12) receptor (P2Y(12)R) is an ADP-activated G protein-coupled receptor (GPCR) that is an important target for antithrombotic drugs.
178	21461952	Three homology models of P2Y(12)R were compared, based on different GPCR structural templates: bovine rhodopsin (bRHO), human A(2A) adenosine receptor (A(2A)AR), and human C-X-C chemokine receptor type 4 (CXCR4).
179	21474712	OCTR-1, a putative octopamine G protein-coupled catecholamine receptor (GPCR, G protein-coupled receptor), functioned in sensory neurons designated ASH and ASI to actively suppress innate immune responses by down-regulating the expression of noncanonical UPR genes pqn/abu in nonneuronal tissues.
180	21958333	The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1.
181	21958333	The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes.
182	21958333	Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors.
183	21958333	Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants.
184	21958333	Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice.
185	21958333	Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance.
186	21958333	Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion.
187	21958333	The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1.
188	21958333	The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes.
189	21958333	Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors.
190	21958333	Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants.
191	21958333	Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice.
192	21958333	Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance.
193	21958333	Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion.
194	21958333	The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) stimulate glucose-induced insulin secretion; however, in patients with type 2 diabetes, the incretin system is impaired by loss of the insulinotropic effects of GIP as well as a possible reduction in secretion of GLP-1.
195	21958333	The currently available incretin-based therapies, GLP-1 receptor agonists (incretin mimetics) and dipeptidyl peptidase-4 (DPP-4) inhibitors (CD26 antigen inhibitors) [incretin enhancers], are safe and effective in the treatment of type 2 diabetes.
196	21958333	Therapies that directly target intestinal L cells to stimulate secretion of endogenous GLP-1 could possibly prove more effective than treatment with GLP-1 receptor agonists and DPP-4 inhibitors.
197	21958333	Potential new approaches to modifying intestinal GLP-1 secretion in patients with type 2 diabetes include G-protein-coupled receptor (GPCR) agonists, α-glucosidase inhibitors, peroxisome proliferator-activated receptor (PPAR) agonists, metformin, bile acid mimetics and bile acid sequestrants.
198	21958333	Both the GPCR agonist AR231453 and the novel bile acid mimetic INT-777 have been shown to stimulate GLP-1 release, leading to increased insulin secretion and improved glucose tolerance in mice.
199	21958333	Similarly, a study in insulin-resistant rats demonstrated that the bile acid sequestrant colesevelam increased GLP-1 secretion and improved glucose levels and insulin resistance.
200	21958333	Evidence suggests that GPCR agonists, α-glucosidase inhibitors, PPAR agonists, metformin, bile acid mimetics and bile acid sequestrants may represent a new approach to management of type 2 diabetes via modification of endogenous GLP-1 secretion.
201	22180093	This gene has been demonstrated to encode a functional receptor of acylation-stimulating protein (ASP), a G-protein-coupled receptor (GPCR), that has been shown to influence insulin secretion in cultured pancreatic islet cells in vitro and is a stimulator of triglyceride synthesis and glucose transport in vivo.
202	22653059	G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice.
203	22653059	We found that the orphan GPCR Gpr21 was highly expressed in the hypothalamus and macrophages of mice and that whole-body KO of this receptor led to a robust improvement in glucose tolerance and systemic insulin sensitivity and a modest lean phenotype.
204	22653059	The improvement in insulin sensitivity in the high-fat diet-fed (HFD-fed) Gpr21 KO mouse was traced to a marked reduction in tissue inflammation caused by decreased chemotaxis of Gpr21 KO macrophages into adipose tissue and liver.
205	22653059	Furthermore, mice lacking macrophage expression of Gpr21 were protected from HFD-induced inflammation and displayed improved insulin sensitivity.
206	22653059	Cumulatively, our data indicate that GPR21 has a critical function in coordinating macrophage proinflammatory activity in the context of obesity-induced insulin resistance.
207	23056280	GPR40 (FFAR1 or FFA1) is a G-protein-coupled receptor (GPCR), primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine.
208	23056280	GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes.
209	23111327	GRK5 ablation contributes to insulin resistance.
210	23111327	The G-protein-coupled receptor kinase 5 (GRK5) is an important member of the threonine/serine kinase family that phosphorylates and regulates the G-protein-coupled receptor (GPCR) signaling pathway.
211	23111327	Insulin resistance is associated with the pathogenesis of metabolic disorders such as type 2 diabetes and obesity; however, the potential role of GRK5 in insulin resistance is unknown.
212	23111327	These mice, which are partially resistant to obesity induced by a high-fat diet, had impaired glucose tolerance and insulin sensitivity, as well as disruption of AKT signaling transduction compared with their wild-type littermates.
213	23111327	Overall, our data identified GRK5 as a positive regulator of insulin sensitivity.
214	23169631	The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes.
215	23169631	However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures.
216	23169631	To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations.
217	23169631	The structure should be useful for guiding drug design and can provide a structural basis for understanding ligand binding and receptor activation of GLP1R and other class B1 GPCRs.
218	23169631	The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes.
219	23169631	However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures.
220	23169631	To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations.
221	23169631	The structure should be useful for guiding drug design and can provide a structural basis for understanding ligand binding and receptor activation of GLP1R and other class B1 GPCRs.
222	23169631	The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes.
223	23169631	However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures.
224	23169631	To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations.
225	23169631	The structure should be useful for guiding drug design and can provide a structural basis for understanding ligand binding and receptor activation of GLP1R and other class B1 GPCRs.
226	23169631	The glucagon-like peptide 1 receptor (GLP1R) is a G protein-coupled receptor (GPCR) involved in insulin synthesis and regulation; therefore, it is an important drug target for treatment of diabetes.
227	23169631	However, GLP1R is a member of the class B1 family of GPCRs for which there are no experimental structures.
228	23169631	To provide a structural basis for drug design and to probe class B GPCR activation, we predicted the transmembrane (TM) bundle structure of GLP1R bound to the peptide Exendin-4 (Exe4; a GLP1R agonist on the market for treating diabetes) using the MembStruk method for scanning TM bundle conformations.
229	23169631	The structure should be useful for guiding drug design and can provide a structural basis for understanding ligand binding and receptor activation of GLP1R and other class B1 GPCRs.
230	23565380	The calcium-sensing receptor (CaSR) is a 1,078 amino acid G protein-coupled receptor (GPCR), which is predominantly expressed in the parathyroids and kidney.
231	23565380	The CaSR allows regulation of parathyroid hormone (PTH) secretion and renal tubular calcium re-absorption in response to alterations in extracellular calcium concentrations.
232	23565380	Loss-of-function CaSR mutations have been reported in the hypercalcemic disorders of familial benign (hypocalciuric) hypercalcemia (FBH or FHH), neonatal severe primary hyperparathyroidism (NSHPT), and adult primary hyperparathyroidism.
233	23696845	Transient and stable expression of the neurotensin receptor NTS1: a comparison of the baculovirus-insect cell and the T-REx-293 expression systems.
234	23696845	Here we constructed a suspension T-REx-293 cell line to stably express an engineered neurotensin receptor 1 (NTS1) mutant and we quantitatively compared this cell line with the transient baculovirus-insect cell system throughout a milligram-scale NTS1 expression and purification process.
235	23696845	This work demonstrates two approaches for preparing milligram quantities of purified NTS1 suitable for structural studies and provides useful input to users in choosing and optimizing an appropriate expression host for other GPCRs.
236	23856265	The extracellular calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor (GPCR) that is expressed at multiple sites, including the parathyroids and kidneys.
237	23856265	Moreover, autoantibodies directed against the extracellular domain of the CaSR have been found to be associated with FHH in some patients, and also in some patients with hypoparathyroidism that may be part of autoimmune polyglandular syndrome type 1.
238	23862620	In the past half decade, deorphanization of several GPCRs has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various carbon chain lengths.
239	23862620	GPR40 and GPR120 are activated by medium- and long-chain FFAs.
240	23862620	GPR41 and GPR43 are activated by short-chain FFAs.
241	23862620	GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion.
242	23862620	GPR120 is mainly expressed in enteroendocrine cells and plays an important role for FFAs-induced glucagon-like peptide-1.
243	23862620	GPR43 is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes.
244	22821234	Mutational modification of distinct muscarinic receptor subtypes has yielded novel designer G protein-coupled receptors (GPCRs) that are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound.
245	22821234	These CNO-sensitive designer GPCRs [alternative name: designer receptors exclusively activated by designer drug (DREADDs)] have emerged as powerful new tools to dissect the in vivo roles of distinct G protein signaling pathways in specific cell types or tissues.
246	22821234	As is the case with other GPCRs, CNO-activated DREADDs not only couple to heterotrimeric G proteins but can also recruit proteins of the arrestin family (arrestin-2 and -3).
247	22821234	In this study, we describe the development of an M₃ muscarinic receptor-based DREADD [Rq(R165L)] that is no longer able to couple to G proteins but can recruit arrestins and promote extracellular signal-regulated kinase-1/2 phosphorylation in an arrestin- and CNO-dependent fashion.
248	22821234	Moreover, CNO treatment of mouse insulinoma (MIN6) cells expressing the Rq(R165L) construct resulted in a robust, arrestin-dependent stimulation of insulin release, directly implicating arrestin signaling in the regulation of insulin secretion.
249	22821234	Mutational modification of distinct muscarinic receptor subtypes has yielded novel designer G protein-coupled receptors (GPCRs) that are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound.
250	22821234	These CNO-sensitive designer GPCRs [alternative name: designer receptors exclusively activated by designer drug (DREADDs)] have emerged as powerful new tools to dissect the in vivo roles of distinct G protein signaling pathways in specific cell types or tissues.
251	22821234	As is the case with other GPCRs, CNO-activated DREADDs not only couple to heterotrimeric G proteins but can also recruit proteins of the arrestin family (arrestin-2 and -3).
252	22821234	In this study, we describe the development of an M₃ muscarinic receptor-based DREADD [Rq(R165L)] that is no longer able to couple to G proteins but can recruit arrestins and promote extracellular signal-regulated kinase-1/2 phosphorylation in an arrestin- and CNO-dependent fashion.
253	22821234	Moreover, CNO treatment of mouse insulinoma (MIN6) cells expressing the Rq(R165L) construct resulted in a robust, arrestin-dependent stimulation of insulin release, directly implicating arrestin signaling in the regulation of insulin secretion.
254	22821234	Mutational modification of distinct muscarinic receptor subtypes has yielded novel designer G protein-coupled receptors (GPCRs) that are unable to bind acetylcholine (ACh), the endogenous muscarinic receptor ligand, but can be efficiently activated by clozapine-N-oxide (CNO), an otherwise pharmacologically inert compound.
255	22821234	These CNO-sensitive designer GPCRs [alternative name: designer receptors exclusively activated by designer drug (DREADDs)] have emerged as powerful new tools to dissect the in vivo roles of distinct G protein signaling pathways in specific cell types or tissues.
256	22821234	As is the case with other GPCRs, CNO-activated DREADDs not only couple to heterotrimeric G proteins but can also recruit proteins of the arrestin family (arrestin-2 and -3).
257	22821234	In this study, we describe the development of an M₃ muscarinic receptor-based DREADD [Rq(R165L)] that is no longer able to couple to G proteins but can recruit arrestins and promote extracellular signal-regulated kinase-1/2 phosphorylation in an arrestin- and CNO-dependent fashion.
258	22821234	Moreover, CNO treatment of mouse insulinoma (MIN6) cells expressing the Rq(R165L) construct resulted in a robust, arrestin-dependent stimulation of insulin release, directly implicating arrestin signaling in the regulation of insulin secretion.