EVIDENCE FOR THE PRESENCE OF CB2-LIKE CANNABINOID RECEPTORS ON PERIPHERAL-NERVE TERMINALS

We have investigated whether there are cannabinoid CB2 receptors that can mediate cannabinoid-induced inhibition of electrically evoked cont ractions in the mouse vas deferens or guinea-pig myenteric plexus-long itudinal muscle preparation. Our results showed that mouse vas deferen s and guinea-pig whole gut contain cannabinoid CB1 and CB2-like mRNA w hereas the myenteric plexus preparation seemed to contain only cannabi noid CB1 mRNA. JWH-015 (1-propyl-2-methyl-3-(1-naphthoyl)indole and JW H-051 oxy-Delta(8)-tetrahydrocannabinol-dimethylheptyl), which have hi gher affinities for CB2 than CB1 cannabinoid binding sites, inhibited electrically evoked contractions of both tissues in a concentration re lated manner. This inhibition was attenuated by 31.62 nM of the cannab inoid CB1 receptor selective antagonist SR141716A dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide hydrochloride] only in the myenteric pl exus preparation. Vasa deferentia from Delta(9)-tetrahydrocannabinol-p retreated mice (20 mg/kg i.p. once daily for two days) showed reduced sensitivity to JWH-015 and JWH-051. The results suggest that these com pounds exert their inhibitory effects through cannabinoid CB1 receptor s in the myenteric plexus preparation, but mainly through CB2-like can nabinoid receptors in the vas deferens. (C) 1997 Elsevier Science B.V.