GPR18 gene

The GPR18 gene (G Protein-Coupled Receptor 18 gene) is a protein-coding gene located on chromosome 13q32.3. G protein-coupled receptors (GPCRs) form the largest receptor family, transduce environmental stimuli into changes in cell behavior, and are important drug targets. Many GPCRs, including GRP18, are classified as orphan receptors due to limited knowledge about their ligands and their coupling to cellular signaling mechanisms (Morri M et al. 2018)

GPR18 encodes a receptor protein, the endocannabinoid N-arachidonylglycine (NAGly ). This receptor can also be activated by herbal and synthetic cannabinoid agonists e.g. 9 -tetrahydrocannabinol (THC=dronabinol) (Miller S et al. 2018). For example, THC lowers intraocular pressure by activating GPR18 (and CB1).

1. Chiang N et al. (2015) Identification of resolvin D2 receptor mediating resolution of infections and organ protection. J Exp Med 212: 1203-1217
2. Miller S et al (2018) Δ9-Tetrahydrocannabinol and Cannabidiol Differentially Regulate Intraocular Pressure. Invest Ophthalmol Vis Sci 59:5904-5911.
3. Morales P et al (2020) Therapeutic Exploitation of GPR18: Beyond the Cannabinoids? J Med Chem 63:14216-14227.
4. Morri M et al (2018) Optical functionalization of human class A orphan G-protein-coupled receptors. Nat Commun 9:1950.
5. Wang X et al (2014) GPR18 is required for a normal CD8αα intestinal intraepithelial lymphocyte compartment. J Exp Med 211:2351-2359