Tuyển tập các báo cáo nghiên cứu khoa học quốc tế về bệnh thú y đề tài: SR144528 as Inverse Agonist of CB2 Cannabinoid Receptor | J. Vet. Sci. 2002 3 3 179-184 JOURNAL OF Veterinary Science SR144528 as Inverse Agonist of CB2 Cannabinoid Receptor Man-Hee Rhee and Sang-Keun Kim1 Dept. of Cell Biology Physiology Washington Univ. School of Medicine 1 College of Vet. Med. Chungnam National University Daejon 305-764 Korea Received May 23 2002 Accepted August 28 2002 Abstract It is now well established that several G protein-coupled receptors can signal without agonist stimulation constitutive receptors . Inverse agonists have been shown to inhibit the activity of such constitutive G protein-coupled receptor signaling. Agonist activation of the Gị o-coupled peripheral cannabinoid receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl cyclase type II. Using transfected COS cells we show here that application of SR144528 an inverse agonist of CB2 leads to a reverse action stimulation of adenylyl cyclase V and inhibition of adenylyl cyclase II . This inverse agonism of SR144528 is dependent on the temperature as well as on the concentration of the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl cyclase activity by SR 144528. Key Words Cannabinoids CB2 cannabinoid receptor SR144528 Inverse agonism G protein Adenylyl cyclase. Introduction Two cannabinoid receptor subtypes referred to as CB1 and CB2 have been cloned so far Matsuda et al. 1990 Munro et al. 1993 . Both receptors belong to the heptahelical G protein-coupled receptor GPCR family and were found to inhibit and stimulate the activity of certain isozymes of adenylyl cyclase AC Rhee et al. 1998 and to stimulate mitogen-activated protein kinase MAPK activity Bouaboula et al. 1995 Bouaboula et al. 1996 . All these actions appear to be exerted through a pertussis toxin PTX -sensitive Gi protein. Receptor-mediated activation of the G protein results in the exchange of tightly-bound GDP for GTP on the G protein a subunit followed by dissociation of the GTP-coupled a a subunits from the ÍỈỴ dimmers .
