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G protein-coupled receptor 18
Symbol GPR18
External IDs OMIM602042 MGI107859 HomoloGene18814 IUPHAR: GPR18 GeneCards: GPR18 Gene
RNA expression pattern
PBB GE GPR18 210279 at tn.png
More reference expression data
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:
99.91 – 99.91 Mb
Chr 14:
121.91 – 121.92 Mb
PubMed search [1] [2]

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



  1. ^ Gantz I, et al. (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, et al. (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. ^ a b McHugh D, et al. (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, 3rd; 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. 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, J. C. (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.  edit
  10. ^ McHugh, D.; Bradshaw, H. B. (2013). "GPR18 and NAGly Signaling: New Members of the Endocannabinoid Family or Distant Cousins?". EndoCANNABINOIDS. p. 135. doi:10.1007/978-1-4614-4669-9_6. ISBN 978-1-4614-4668-2.  edit

Further reading[edit]