GPR18 receptor

The GPR-18 receptor also known as N-arachidonyl-glycinereceptor (NAGlyreceptor ) is a receptor protein that in humans is encoded by the GPR18 gene located on chromosome 13q32.3. The receptor protein has 7 putative transmembrane domains. It shares less than 34% amino acid similarity with other GPCRs.

The activity of this receptor is mediated by G proteins that inhibit adenylyl cyclase. Ligand of this receptor is the endocannabinoid N-arachidonylglycine (NAGly). Furthermore, it can also be activated by plant and synthetic cannabinoid agonists.

The GPR18 protein is most abundant in human testis and spleen. It is also expressed in several other tissues, such as on polymorphonuclear leukocytes, on monocytes and macrophages (Chiang et al. 2015).

Along with the other previously "orphaned" receptors GPR55 and GPR119 , GPR18 was found to be a receptor for endogenous lipid neurotransmitters, some of which also bind to cannabinoid receptors. The GPR18 receptor plays a role in lowering intraocular pressure and blood pressure (Miller S et al. 2018). An important paralogous gene is GPR17.

An activating ligand for GPR18 is resolvin D2. Its activation leads to suppression of inflammatory responses. In addition, RvD2 is a metabolite of the omega-3 fatty acid docosahexaenoic acid (DHA). This metabolism, as well as the activation of GPR18 by RvD2, is thought to be one of the mechanisms responsible for the anti-inflammatory effects attributed to an omega-3 fatty acid-rich diet.