N-arachidonoyl glycine, another endogenous agonist of GPR55

Interest in lipoamino acids as endogenous modulators of G-protein coupled receptors has escalated due to their involvement in a variety of physiologic processes. In particular, a role for these amino acid conjugates has emerged in the endocannabinoid system. The study presented herein investigated the effects of N-arachidonoyl glycine (NAGIy) on a candidate endocannabinoid receptor, GPR55. Our novel findings reveal that NAGIy induces concentration dependent increases in calcium mobilization and mitogen-activated protein kinase activities in HAGPR55/CHO cells. These increases were attenuated by the selective GPR55 antagonist ML193 (N44-[[(3,4-Dimethy1-5-isoxazolyl)amino]sulfonyl1Pheny1]-6,8-dimethy1-2-(2-pyridiny1)-4-quinolinecarboxamide), supporting receptor mediated signaling. To our knowledge this is the first report identifying GPR55 as a target of the endogenous lipoamino acid, NAGIy. (C) 2017 Elsevier Inc. All rights reserved.