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GPR119
Identifiers
Aliases GPR119, GPCR2, G protein-coupled receptor 119
External IDs OMIM: 300513 MGI: 2668412 HomoloGene: 18670 GeneCards: GPR119
Orthologs
SpeciesHumanMouse
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: 130.38 – 130.39 Mb Chr X: 47.76 – 47.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the GPR119 gene. [5]

GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors. [6] [7] [8]

Pharmacology

GPR119 is expressed predominantly in the pancreas and gastrointestinal tract in rodents and humans, as well as in the brain in rodents. [9] Activation of the receptor has been shown to cause a reduction in food intake and body weight gain in rats. [9] GPR119 has also been shown to regulate incretin and insulin hormone secretion. [10] [11] [12] As a result, new drugs acting on the receptor have been suggested as novel treatments for obesity and diabetes. [9] [11] [13]

Ligands

A number of endogenous, synthetic and plant derived ligands for this receptor have been identified: [14] [15] [16]

Human microbiota and GPR119 activation

Commensal bacteria are found to have important roles in human health, as bacterial metabolites are likely to be key components of host interactions by which they affect mammalian physiology. [20] N-acyl amide synthase genes are found enriched in gastrointestinal bacteria and the lipids, that they encode, interact with GPCRs, which regulate gastrointestinal tract physiology, where cell-based models have demonstrated, that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, and the clearest overlap in structure and function between bacterial and human GPCR-active ligands, is found for the endocannabinoid receptor GPR119. [21]

The experiment have isolated both the palmitoyl and oleoyl analogs of N-acyl serinol, and found the latter only differs from 2-OG: C21H40O4 by the presence of an amide instead of an ester, and from OEA: C20H39NO2 by the presence of an additional ethanol substituent, where the N-oleoyl serinol (C21H41NO3; 18: 1, n-9), [22] is a similarly potent GPR119 agonist compared to the endogenous ligand OEA ( EC50 12 µM vs. 7 µM), but elicits almost a 2-fold greater maximum activation, do suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria, [21] that communicate through interactions between these two fundamental systems—which form the gut microbiota- endocannabinoidome axis. [20]

Evolution

Paralogues

Source: [23]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000147262 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000051209 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: GPR119 G protein-coupled receptor 119".
  6. ^ a b c Brown AJ (November 2007). "Novel cannabinoid receptors". British Journal of Pharmacology. 152 (5): 567–575. doi: 10.1038/sj.bjp.0707481. PMC  2190013. PMID  17906678.
  7. ^ 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.
  8. ^ McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel 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.
  9. ^ a b c d e f Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, et al. (March 2006). "Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents". Cell Metabolism. 3 (3): 167–175. doi: 10.1016/j.cmet.2006.02.004. PMID  16517404.
  10. ^ a b c Ning Y, O'Neill K, Lan H, Pang L, Shan LX, Hawes BE, Hedrick JA (December 2008). "Endogenous and synthetic agonists of GPR119 differ in signalling pathways and their effects on insulin secretion in MIN6c4 insulinoma cells". British Journal of Pharmacology. 155 (7): 1056–1065. doi: 10.1038/bjp.2008.337. PMC  2528830. PMID  18724386.
  11. ^ a b Swaminath G (December 2008). "Fatty acid binding receptors and their physiological role in type 2 diabetes". Archiv der Pharmazie. 341 (12): 753–761. doi: 10.1002/ardp.200800096. PMID  19009545. S2CID  6933463.
  12. ^ Lan H, Vassileva G, Corona A, Liu L, Baker H, Golovko A, et al. (May 2009). "GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis". The Journal of Endocrinology. 201 (2): 219–230. doi: 10.1677/JOE-08-0453. PMID  19282326.
  13. ^ a b c Overton HA, Fyfe MC, Reynet C (March 2008). "GPR119, a novel G protein-coupled receptor target for the treatment of type 2 diabetes and obesity". British Journal of Pharmacology. 153 (Suppl 1): S76–S81. doi: 10.1038/sj.bjp.0707529. PMC  2268073. PMID  18037923.
  14. ^ 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): 519–532. PMID  19562648.
  15. ^ Godlewski G, Offertáler L, Wagner JA, Kunos G (September 2009). "Receptors for acylethanolamides-GPR55 and GPR119". Prostaglandins & Other Lipid Mediators. 89 (3–4): 105–111. doi: 10.1016/j.prostaglandins.2009.07.001. PMC  2751869. PMID  19615459.
  16. ^ Wu Y, Kuntz JD, Carpenter AJ, Fang J, Sauls HR, Gomez DJ, et al. (April 2010). "2,5-Disubstituted pyridines as potent GPR119 agonists". Bioorganic & Medicinal Chemistry Letters. 20 (8): 2577–2581. doi: 10.1016/j.bmcl.2010.02.083. PMID  20227877.
  17. ^ Hansen KB, Rosenkilde MM, Knop FK, Wellner N, Diep TA, Rehfeld JF, et al. (September 2011). "2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans". The Journal of Clinical Endocrinology and Metabolism. 96 (9): E1409–E1417. doi: 10.1210/jc.2011-0647. PMID  21778222.
  18. ^ Semple G, Fioravanti B, Pereira G, Calderon I, Uy J, Choi K, et al. (September 2008). "Discovery of the first potent and orally efficacious agonist of the orphan G-protein coupled receptor 119". Journal of Medicinal Chemistry. 51 (17): 5172–5175. doi: 10.1021/jm8006867. PMID  18698756.
  19. ^ Jones RM, Leonard JN, Buzard DJ, Lehmann J (October 2009). "GPR119 agonists for the treatment of type 2 diabetes". Expert Opinion on Therapeutic Patents. 19 (10): 1339–1359. doi: 10.1517/13543770903153878. PMID  19780700. S2CID  33083682.
  20. ^ a b Lacroix, Sébastien (2019-12-17). "Rapid and Concomitant Gut Microbiota and Endocannabinoidome Response to Diet-Induced Obesity in Mice". mSystems. 4 (6): e00407-19. doi: 10.1128/mSystems.00407-19. PMC  6918026. PMID  31848310.
  21. ^ a b Cohen, Louis J. (2017-09-07). "Commensal bacteria produce GPCR ligands that mimic human signaling molecules". Nature. 549 (7670): 48–53. doi: 10.1038/nature23874. PMC  5777231. PMID  28854168.
  22. ^ PubChem. "n-Oleoyl serinol". pubchem.ncbi.nlm.nih.gov. Retrieved 2023-06-13.
  23. ^ "GeneCards®: The Human Gene Database".

Further reading

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