Biology:NAGly receptor

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


N-Arachidonyl glycine receptor (NAGly receptor), also known as G protein-coupled receptor 18 (GPR18), is a protein that in humans is encoded by the GPR18 gene.[1][2] Along with the other previously "orphan" receptors GPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors.[3][4][5] It has been found to be involved in the regulation of intraocular pressure.[6]

Research supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglial migration in the CNS through activation of GPR18,[7] though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons.[8]

Resolvin D2 (RvD2), a member of the specialized proresolving mediators (SPM) class of polyunsaturated fatty acid metabolites, is an activating ligand for GPR18; RvD2 and its activation of GPR18 contribute to the resolution of inflammatory responses as well as inflammation-based and other diseases in animal models and are proposed to do so in humans.[9] Furthermore, RvD2 is a metabolite of the omega-3 fatty acid, docosahexaenoic acid (DHA); the metabolism of DHA to RvD2 and RvD2's activation of GPR18 is proposed to one among many other mechanisms for the anti-inflammatory and other beneficial effects attributed to omega-3 fatty acid-rich diets[10]

Ligands

Agonists

Ligands found to bind to GPR18 as agonists include:[7][11]

Antagonists

References

  1. ↑ "Cloning and chromosomal localization of a gene (GPR18) encoding a novel seven transmembrane receptor highly expressed in spleen and testis". Genomics 42 (3): 462–6. Sep 1997. doi:10.1006/geno.1997.4752. PMID 9205118. 
  2. ↑ "Entrez Gene: GPR18 G protein-coupled receptor 18". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2841. 
  3. ↑ "Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18". Biochem. Biophys. Res. Commun. 347 (3): 827–32. September 2006. doi:10.1016/j.bbrc.2006.06.175. PMID 16844083. 
  4. ↑ Burstein S (December 2008). "The elmiric acids: biologically active anandamide analogs". Neuropharmacology 55 (8): 1259–64. doi:10.1016/j.neuropharm.2007.11.011. PMID 18187165. 
  5. ↑ "Orphan endogenous lipids and orphan GPCRS: A good match". Prostaglandins Other Lipid Mediat. 89 (3–4): 131–4. September 2009. doi:10.1016/j.prostaglandins.2009.04.006. PMID 19379823. 
  6. ↑ "A GPR18-based signalling system regulates IOP in murine eye". British Journal of Pharmacology 169 (4): 834–43. June 2013. doi:10.1111/bph.12136. PMID 23461720. 
  7. ↑ 7.0 7.1 "N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor". BMC Neurosci 11: 44. 2010. doi:10.1186/1471-2202-11-44. PMID 20346144. 
  8. ↑ "N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways.". Molecular Pharmacology 83 (1): 267–82. Jan 2013. doi:10.1124/mol.112.081182. PMID 23104136. 
  9. ↑ "Novel Endogenous Proresolving Molecules:Essential Fatty Acid-Derived and Gaseous Mediators in the Resolution of Inflammation". Journal of Atherosclerosis and Thrombosis 23 (6): 655–64. 2016. doi:10.5551/jat.33928. PMID 27052783. 
  10. ↑ "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1851 (4): 469–84. 2015. doi:10.1016/j.bbalip.2014.08.010. PMID 25149823. 
  11. ↑ "Δ(9) -THC and N-arachidonyl glycine are full agonists at GPR18 and cause migration in the human endometrial cell line, HEC-1B". Br J Pharmacol 165 (8): 2414–24. May 2011. doi:10.1111/j.1476-5381.2011.01497.x. PMID 21595653. 
  12. ↑ "Nonpsychotropic cannabinoids, abnormal cannabidiol and canabigerol-dimethyl heptyl, act at novel cannabinoid receptors to reduce intraocular pressure". Journal of Ocular Pharmacology and Therapeutics 27 (5): 427–35. October 2011. doi:10.1089/jop.2011.0041. PMID 21770780. 
  13. ↑ Ashton JC (2012). "The atypical cannabinoid o-1602: Targets, actions, and the central nervous system". Central Nervous System Agents in Medicinal Chemistry 12 (3): 233–239. doi:10.2174/187152412802430156. PMID 22831390. 
  14. ↑ Abood ME, ed (2012). "GPR18 and NAGly Signaling: New Members of the Endocannabinoid Family or Distant Cousins?". endoCANNABINOIDS: actions at non-CB1/CB2 cannabinoid receptors. New York: Springer. ISBN 978-1-4614-4668-2. 
  15. ↑ "Identification of Resolvin D2 Receptor Mediating Resolution of Infections and Organ Protection". J. Exp. Med. 212 (8): 1203–1217. 2015. doi:10.1084/jem.20150225. PMID 26195725. PMC 4516788. https://dash.harvard.edu/bitstream/handle/1/24983913/4516788.pdf?sequence=1. 
  16. ↑ "Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18". European Journal of Medicinal Chemistry 155: 381–397. July 2018. doi:10.1016/j.ejmech.2018.05.050. PMID 29902723. 
  17. ↑ "Bicyclic imidazole-4-one derivatives: a new class of antagonists for the orphan G protein-coupled receptors GPR18 and GPR55". Med. Chem. Commun. 5 (5): 632–649. 2014. doi:10.1039/C3MD00394A. 

Further reading

  • "An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia". Genomics 79 (5): 635–56. 2002. doi:10.1006/geno.2002.6765. PMID 11991713. 
  • "Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18". Biochem. Biophys. Res. Commun. 347 (3): 827–32. 2006. doi:10.1016/j.bbrc.2006.06.175. PMID 16844083. 




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