Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin

The identification of molecular targets of bioactive food components is important to understand the mechanistic aspect of their physiological functions. Here, we have developed a screening system that enables us to determine the activation of G protein-coupled receptors (GPCRs) by food components and have identified GPR55 as a target for curcumin. Curcumin activated GPR55 and induced serum-response element- and serum-response factor-mediated transcription, which were inhibited by Rho kinase and GPR55 antagonists. Both the methoxy group and the heptadienone moiety of curcumin were required for GPR55 activation. The F190^5.47 residue of GPR55 was important for the interaction with curcumin. The curcumin-induced secretion of glucagon-like peptide-1 in GLUTag cells was inhibited by a GPR55 antagonist. These results indicate that expression screening is a useful system to identify GPCRs as targets of food components and strongly suggest that curcumin activates GPR55 as an agonist, which is involved in the physiological function of curcumin.