GPR18

G protein-coupled receptor 18
Identifiers
Symbol	GPR18
External IDs	OMIM: 602042 MGI: 107859 HomoloGene: 18814 IUPHAR: 89 GeneCards: GPR18 Gene
Gene ontology Molecular function • G-protein coupled receptor activity Cellular component • plasma membrane • integral component of membrane Biological process • G-protein coupled receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2841	110168
Ensembl	ENSG00000125245	ENSMUSG00000050350
UniProt	Q14330	Q8K1Z6
RefSeq (mRNA)	NM_001098200	NM_182806
RefSeq (protein)	NP_001091670	NP_877958
Location (UCSC)	Chr 13: 99.25 – 99.26 Mb	Chr 14: 121.91 – 121.92 Mb
PubMed search

N-arachidonyl glycine 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]

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,^[6] though recent evidence demonstrates that NAGly was not shown to be a GPR18 agonist in rat sympathetic neurons.^[7]

Ligands

Agonists

Ligands found to bind to GPR18 as agonists include:^[6][8]

• N-Arachidonoylglycine (NAGly)
• Abnormal cannabidiol (Abn-CBD)
• AM-251 - partial agonist
• Cannabidiol - partial agonist
• O-1602
• Δ⁹-Tetrahydrocannabinol (Δ⁹-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.^[9]
• Anandamide (N-arachidonoyl ethanolamine, AEA)
• Arachidonylcyclopropylamide (ACPA)^[10]
• Resolvin D2 (RvD2) ^[11]

Antagonists

• O-1918
• CID-85469571 ^[12]

References

1. 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. PMID 9205118.
2. "Entrez Gene: GPR18 G protein-coupled receptor 18".
3. 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. 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. PMC 2621443. PMID 18187165.
5. Bradshaw HB, Lee SH, McHugh D (September 2009). "ORPHAN ENDOGENOUS LIPIDS AND ORPHAN GPCRS: A GOOD MATCH". Prostaglandins Other Lipid Mediat. 89 (3–4): 131–4. doi:10.1016/j.prostaglandins.2009.04.006. PMC 2740803. PMID 19379823.
6. McHugh D, Hu SS, Rimmerman N, Juknat A, Vogel Z, Walker JM, Bradshaw HB (2010). "N-arachidonoyl glycine, an abundant endogenous lipid, potently drives directed cellular migration through GPR18, the putative abnormal cannabidiol receptor". BMC Neurosci 11: 44. doi:10.1186/1471-2202-11-44. PMC 2865488. PMID 20346144.
7. Lu VB, Puhl HL, Ikeda SR (Jan 2013). "N-Arachidonyl glycine does not activate G protein-coupled receptor 18 signaling via canonical pathways.". Molecular Pharmacology 83 (1): 267–82. doi:10.1124/mol.112.081182. PMC 3533477. PMID 23104136.
8. McHugh D, Page J, Dunn E, Bradshaw HB (May 2011). "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): no. doi:10.1111/j.1476-5381.2011.01497.x. PMID 21595653.
9. 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.
10. McHugh D, Bradshaw HB (2012). "GPR18 and NAGly Signaling: New Members of the Endocannabinoid Family or Distant Cousins?". In Abood ME. endoCANNABINOIDS: actions at non-CB1/CB2 cannabinoid receptors. New York: Springer. ISBN 978-1-4614-4668-2.
11. Chiang N, Dalli J, Colas RA, Serhan CN (2015). "Identification of Resolvin D2 Receptor Mediating Resolution of Infections and Organ Protection". J. Exp. Med. 212 (8): 1203–1217. doi:10.1084/jem.20150225. PMID 26195725.
12. Rempel, V; 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: 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. PMID 11991713.
• 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. PMID 16844083.