G protein-coupled receptor 18 orphan (IPR028335)

Short name: GPR18

Overlapping homologous superfamilies


Family relationships


Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. However, recent research has identified certain pharmacological targets that could be investigated to find, for example, new potential cannabinoid receptors or channels [PMID: 21079038, PMID: 17906678, PMID: 20117132]. GPR18 IPR028335 [PMID: 21595653, PMID: 20346144], GPR55 IPR028334 [PMID: 17876302, PMID: 17876300], GPR119 IPR028336 [PMID: 20117132] show little structural similarity to CB1 and CB2 receptors, but they respond to endogenous agents analogous to the endogenous cannabinoid ligands, as well as some natural/synthetic cannabinoid receptor ligands [PMID: 21079038]. However, because they do not fulfill all of the cannabinoid receptor criteria defined by IUPHAR, the classification of these proteins remains a contentious issue due to conflicting pharmacological results. As a result, they remain classified as putative endogenous agonists by IUPHAR [PMID: 21079038].

This entry represents G protein-coupled receptor 18, also known as N-arachidonyl glycine receptor. It has been found to be a receptor for endogenous lipid neurotransmitters, several of which also bind to cannabinoid receptors [PMID: 21595653, PMID: 16844083, PMID: 18187165, PMID: 19379823]. Recent research also 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 [PMID: 20346144]. However, the pairing of GPR18 with N-arachidonoylglycine (NAGly) and tetrahydrocannabinol (THC) was not reproduced in two studies based on beta-arrestin assays [PMID: 23396314, PMID: 19286662]. So, until further research allows a more definitive decision the function and nomenclature GPR18 is still being debated [PMID: 22014123, PMID: 23686350].

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.