GPR35

GPR35 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in the gastrointestinal (GI) tract, predominantly in colon epithelial cells (CEC). Kynurenic acid, a metabolite of L-tryptophan, has been proposed to be the endogenous ligand of GPR3535. Upon kynurenic acid-mediated GPR35 activation, β-arrestin 2 translocates to the cell membrane to mediate GPR35 internalization, resulting in receptor desensitization. Single nucleotide polymorphisms of GPR35 have linked this receptor to inflammatory bowel disease and primary sclerosing cholangitis, suggesting a role in gastrointestinal inflammation. In addition, in conjunction with previous findings that link agonism of GPR35 with significant reduction in nociceptive pain, GPR35 has emerged as a potential effector of regulation of mechanical sensitivity and analgesia of the Ret tyrosine kinase, and as a receptor involved in the transmission of anti-inflammatory effects of aspirin– potentially through affecting leukocyte rolling, adhesion and extravasation.