Agonist activation of the G protein-coupled receptor GPR35 involves transmembrane domain III and is transduced via Galpha13 and beta-arrestin-2

These studies indicate that I?-arrestin-2 interaction assays are highly appropriate to explore the pharmacology of GPR35 and that GI?13 activation is an alternative avenue of signal generation from GPR35. Arginine and tyrosine residues in transmembrane domain III are integral to agonist recognition and function of this receptor. The potency of kynurenic acid at human GPR35 is sufficiently low, however, to question whether it is likely to be the true endogenous ligand for this receptor.