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.[5][6] 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.[7][8][9] It has been found to be involved in the regulation of intraocular pressure.[10]
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,[11] though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons.[12]
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.[13] 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[14]
^"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.
^Gantz I, Muraoka A, Yang YK, Samuelson LC, Zimmerman EM, Cook H, Yamada T (Sep 1997). "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. doi:10.1006/geno.1997.4752. PMID9205118.
^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.