GPR119

From Wikipedia, the free encyclopedia

G protein-coupled receptor 119

Identifiers

External IDs

OMIM: 300513 MGI: 2668412 HomoloGene: 18670 IUPHAR: GPR119 ChEMBL: 5652 GeneCards: GPR119 Gene

Gene Ontology
Molecular function	• G-protein coupled receptor activity • phosphatidylcholine binding
Cellular component	• plasma membrane • integral to membrane
Biological process	• insulin secretion
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr X:
129.52 – 129.52 Mb

Chr X:
48.67 – 48.67 Mb

PubMed search

G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene.^[1]

GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors.^[2]^[3]^[4]

Pharmacology

GPR119 is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents.^[5] Activation of the receptor has been shown to cause a reduction in food intake and body weight gain in rats.^[5] GPR119 has also been shown to regulate incretin and insulin hormone secretion.^[6]^[7]^[8] As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes.^[5]^[7]^[9]

Ligands

A number of endogenous and synthetic ligands for this receptor have been identified:^[10]^[11]^[12]

2-Oleoylglycerol ^[13]
Anandamide^[9]
AR-231,453^[14]
MBX-2982^[15]
Oleoylethanolamide^[2]^[9]^[5] (Endogenous Ligand) ^[2]
PSN-375,963^[5]^[6]
PSN-632,408^[5]^[6]

References

↑ "Entrez Gene: GPR119 G protein-coupled receptor 119".
↑ 2.0 2.1 2.2 Brown AJ (November 2007). "Novel cannabinoid receptors". Br. J. Pharmacol. 152 (5): 567–75. doi:10.1038/sj.bjp.0707481. PMC 2190013. PMID 17906678.
↑ Izzo AA, Sharkey KA (April 2010). "Cannabinoids and the gut: new developments and emerging concepts". Pharmacology & Therapeutics 126 (1): 21–38. doi:10.1016/j.pharmthera.2009.12.005. PMID 20117132.
↑ McHugh D, Hu SS, Rimmerman N, Juknat A, Vogil Z, Walker JM, Bradshaw HB (March 2010). "N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor". BMC Neuroscience 11: 44. doi:10.1186/1471-2202-11-44. PMC 2865488. PMID 20346144.
↑ 5.0 5.1 5.2 5.3 5.4 5.5 Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, Jackson HC, Procter MJ, Rasamison CM, Tang-Christensen M, Widdowson PS, Williams GM, Reynet C. (2006). "Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents". Cell Metab. 3 (3): 167–75. doi:10.1016/j.cmet.2006.02.004. PMID 16517404.
↑ 6.0 6.1 6.2 Ning Y, O'Neill K, Lan H, Pang L, Shan LX, Hawes BE, Hedrick JA. (2008). "Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells". Br J Pharmacol. 155 (7): 1056–65. doi:10.1038/bjp.2008.337. PMC 2528830. PMID 18724386.
↑ 7.0 7.1 Swaminath G. (2008). "Fatty acid binding receptors and their physiological role in type 2 diabetes". Arch Pharm (Weinheim). 341 (12): 753–61. doi:10.1002/ardp.200800096. PMID 19009545.
↑ Lan H, Vassileva G, Corona A, Liu L, Baker H, Golovko A, Abbondanzo SJ, Hu W, Yang S, Ning Y, Del Vecchio RA, Poulet F, Laverty M, Gustafson EL, Hedrick JA, Kowalski TJ. (2009). "GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis". J Endocrinol. 201 (2): 219–30. doi:10.1677/JOE-08-0453. PMID 19282326.
↑ 9.0 9.1 9.2 Overton HA, Fyfe MC, Reynet C. (2007). "GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity". Br J Pharmacol. 153 (Suppl 1): S76–81. doi:10.1038/sj.bjp.0707529. PMC 2268073. PMID 18037923.
↑ Shah U (July 2009). "GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders". Current Opinion in Drug Discovery & Development 12 (4): 519–32. PMID 19562648.
↑ Godlewski G, Offertáler L, Wagner JA, Kunos G (September 2009). "Receptors for acylethanolamides-GPR55 and GPR119". Prostaglandins & Other Lipid Mediators 89 (3–4): 105–11. doi:10.1016/j.prostaglandins.2009.07.001. PMC 2751869. PMID 19615459.
↑ Wu Y, Kuntz JD, Carpenter AJ, Fang J, Sauls HR, Gomez DJ, Ammala C, Xu Y, Hart S, Tadepalli S (April 2010). "2,5-Disubstituted pyridines as potent GPR119 agonists". Bioorganic & Medicinal Chemistry Letters 20 (8): 2577–81. doi:10.1016/j.bmcl.2010.02.083. PMID 20227877.
↑ Hansen, K. B.; Rosenkilde, M. M.; Knop, F. K.; Wellner, N.; Diep, T. A.; Rehfeld, J. F.; Andersen, U. B.; Holst, J. J.; Hansen, H. S. (2011). "2-Oleoyl Glycerol is a GPR119 Agonist and Signals GLP-1 Release in Humans". Journal of Clinical Endocrinology & Metabolism 96 (9): E1409–E1417. doi:10.1210/jc.2011-0647. PMID 21778222.
↑ Semple G, Fioravanti B, Pereira G, Calderon I, Uy J, Choi K, Xiong Y, Ren A, Morgan M, Dave V, Thomsen W, Unett DJ, Xing C, Bossie S, Carroll C, Chu ZL, Grottick AJ, Hauser EK, Leonard J, Jones RM. (2008). "Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119". J Med Chem. 51 (17): 5172–5. doi:10.1021/jm8006867. PMID 18698756.
↑ Jones RM, Leonard JN, Buzard DJ, Lehmann J (October 2009). "GPR119 agonists for the treatment of type 2 diabetes". Expert Opin Ther Pat 19 (10): 1339–59. doi:10.1517/13543770903153878. PMID 19780700.

Takeda S, Kadowaki S, Haga T et al. (2002). "Identification of G protein-coupled receptor genes from the human genome sequence". FEBS Lett. 520 (1–3): 97–101. doi:10.1016/S0014-5793(02)02775-8. PMID 12044878.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Fredriksson R, Höglund PJ, Gloriam DE et al. (2003). "Seven evolutionarily conserved human rhodopsin G protein-coupled receptors lacking close relatives". FEBS Lett. 554 (3): 381–8. doi:10.1016/S0014-5793(03)01196-7. PMID 14623098.
Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Ross MT, Grafham DV, Coffey AJ et al. (2005). "The DNA sequence of the human X chromosome". Nature 434 (7031): 325–37. doi:10.1038/nature03440. PMC 2665286. PMID 15772651.
Overton HA, Babbs AJ, Doel SM et al. (2006). "Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents". Cell Metab. 3 (3): 167–75. doi:10.1016/j.cmet.2006.02.004. PMID 16517404.

Cell surface receptor: G protein-coupled receptors

Class A:
Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic
glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F:
Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

This article is issued from Wikipedia. The text is available under the Creative Commons Attribution/Share Alike; additional terms may apply for the media files.

GPR119

Pharmacology

Ligands

References

Further reading