GPR119

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G protein-coupled receptor 119
Identifiers
Symbols GPR119 ; GPCR2
External IDs OMIM300513 MGI2668412 HomoloGene18670 IUPHAR: GPR119 ChEMBL: 5652 GeneCards: GPR119 Gene
RNA expression pattern
PBB GE GPR119 gnf1h09789 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 139760 236781
Ensembl ENSG00000147262 ENSMUSG00000051209
UniProt Q8TDV5 Q7TQP3
RefSeq (mRNA) NM_178471 NM_181751
RefSeq (protein) NP_848566 NP_861416
Location (UCSC) Chr X:
129.52 – 129.52 Mb
Chr X:
48.67 – 48.67 Mb
PubMed search [1] [2]

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[edit]

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[edit]

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

References[edit]

  1. ^ "Entrez Gene: GPR119 G protein-coupled receptor 119". 
  2. ^ a b c Brown AJ (November 2007). "Novel cannabinoid receptors". Br. J. Pharmacol. 152 (5): 567–75. doi:10.1038/sj.bjp.0707481. PMC 2190013. PMID 17906678. 
  3. ^ 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. 
  4. ^ 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. ^ a b c d e f 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. ^ a b c 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. ^ a b 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. 
  8. ^ 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. ^ a b c 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. 
  10. ^ 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. 
  11. ^ 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. 
  12. ^ 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. 
  13. ^ 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.  edit
  14. ^ 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. 
  15. ^ 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. 

Further reading[edit]