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(Redirected from GPR18)
Protein-coding gene in the species Homo sapiens
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 GPR18gene. Along with the other previously orphan receptorsGPR55 and GPR119, GPR18 has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors. It has been found to be involved in the regulation of intraocular pressure.
Research supports the hypothesis that GPR18 is the abnormal cannabidiol receptor and N-arachidonoyl glycine, the endogenous lipid metabolite of anandamide, initiates directed microglialmigration in the CNS through activation of GPR18, though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons.
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. 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
Ligands
Agonists
Ligands found to bind to GPR18 as agonists include:
Δ-Tetrahydrocannabinol (Δ-THC) - THC is actually a more potent agonist at GPR18 than at CB1 or CB2, with Ki of 0.96nM at GPR18, 8.1nM at GPR55, 25.1nM at CB1 and 35.2nM at CB2.
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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Kohno M, Hasegawa H, Inoue A, Muraoka M, Miyazaki T, Oka K, Yasukawa M (September 2006). "Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18". Biochem. Biophys. Res. Commun. 347 (3): 827–32. doi:10.1016/j.bbrc.2006.06.175. PMID16844083.
Szczesniak AM, Maor Y, Robertson H, Hung O, Kelly ME (October 2011). "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. doi:10.1089/jop.2011.0041. PMID21770780.
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. PMID22831390.
McHugh D, Bradshaw HB (2012). "GPR18 and NAGly Signaling: New Members of the Endocannabinoid Family or Distant Cousins?". In Abood ME (ed.). endoCANNABINOIDS: actions at non-CB1/CB2 cannabinoid receptors. New York: Springer. ISBN978-1-4614-4668-2.
Schoeder CT, Kaleta M, Mahardhika AB, Olejarz-Maciej A, Łażewska D, Kieć-Kononowicz K, Müller CE (July 2018). "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. doi:10.1016/j.ejmech.2018.05.050. PMID29902723. S2CID49214747.
Rempel V, Atzler K, Behrenswerth A, Karcz T, Schoeder C, Hinz S, et al. (2014). "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. doi:10.1039/C3MD00394A.
Further reading
Christian SL, McDonough J, Liu Cy CY, Shaikh S, Vlamakis V, Badner JA, Chakravarti A, Gershon ES (2002). "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. doi:10.1006/geno.2002.6765. PMID11991713.
Kohno M, Hasegawa H, Inoue A, Muraoka M, Miyazaki T, Oka K, Yasukawa M (2006). "Identification of N-arachidonylglycine as the endogenous ligand for orphan G-protein-coupled receptor GPR18". Biochem. Biophys. Res. Commun. 347 (3): 827–32. doi:10.1016/j.bbrc.2006.06.175. PMID16844083.
