RT Journal Article SR Electronic T1 Cloning and Pharmacological Characterization of the Rat CB2 Cannabinoid Receptor JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 886 OP 894 VO 292 IS 3 A1 Graeme Griffin A1 Qing Tao A1 Mary E. Abood YR 2000 UL http://jpet.aspetjournals.org/content/292/3/886.abstract AB Many of the pharmacological effects of Δ9-tetrahydrocannabinol are mediated through CB1 and CB2 cannabinoid receptors. However, with the discovery of endogenous cannabinoids, some discrepancies have arisen. Furthermore, unlike the CB1 receptor, the sequences of the mouse and human CB2 receptor are divergent, raising the possibility of species specificity. The gene for the rat CB2 receptor was cloned, expressed, and its properties compared with those of mouse and human CB2 receptors. Sequence analysis of the coding region of the rat CB2genomic clone indicates 90% nucleic acid identity (93% amino acid identity) between rat and mouse and 81% nucleic acid identity (81% amino acid identity) between rat and human. The rat CB2receptor was stably expressed in human embryonic kidney-293 cells to examine its pharmacology. The rat CB2 showed low affinity for anandamide, an endogenous ligand shown to act at the CB1 receptor. In contrast, high-affinity binding for SR144528 (CB2-selective antagonist) as well as several cannabinoid receptor agonists was observed. Coupling to adenylate cyclase was observed. Aspects of the pharmacology of palmitoylethanolamide were also examined. It bound to CB1and CB2 receptors with low affinity and stimulated GTPγS binding in the cerebellum and CB2-expressing cell lines with low potency. The data in this study suggest that the discrepancies in affinities between rat and human may represent species differences. The rat CB2 receptor genomic clone will be a useful tool for studying the function and regulation of CB2 in rats. The American Society for Pharmacology and Experimental Therapeutics