G protein-coupled receptor 18
Symbols 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_001098200.1 NM_182806.1
RefSeq (protein) NP_001091670.1 NP_877958.1
Location (UCSC) Chr 13:
99.91 – 99.91 Mb
Chr 14:
122.31 – 122.31 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]

Recent 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]


Ligands found to bind to GPR18 include:[6][7]

  • N-arachidonoyl glycine (NAGly)
  • Abnormal cannabidiol (Abn-CBD)
  • O-1602
  • Δ9-Tetrahydrocannabinol9-THC)
  • Anandamide (N-arachidonoyl ethanolamine, AEA)
  • Arachidonylcyclopropylamide (ACPA)


  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. ^ a b 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. ^ 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: no. doi:10.1111/j.1476-5381.2011.01497.x. PMID 21595653. 

Further reading

Metabolites and
signaling molecules
Class B: Secretin like Class C: Metabotropic
glutamate / pheromone Class F:
Frizzled / Smoothened
B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

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