Defaecation, intestinal fluid accumulation and motility in rodents: implications of cannabinoid CB1 receptors

We have studied the effect of SR141716A (0.1-5 mg/kg, i.p.), a cannabinoid CB1 receptor antagonist, and WIN (0.1-5 mg/kg, i.p.), a cannabinoid recepto r agonist, on acute defaecation and gastrointestinal transit in mice and on intraluminal fluid accumulation in the rat small intestine. SR141716A incr eased while WIN 55,212-2 decreased defaecation, gastrointestinal transit an d fluid accumulation. A per se non-effective dose of SR141716A (0.3 mg/kg) counteracted the inhibitory effect of WIN 55,212-2 (1 mg/kg) on gastrointes tinal functions studied. The effect of SR141716 on both intestinal fluid ac cumulation in rats and gastrointestinal transit in mice was inhibited by at ropine (1 mg/kg, i.p.), but not by hexamethonium (1 mg/kg, s.c.), SR140333 (20 mu g/kg, i.p.) or SR48968 (20 mu g/kg, i.p.), antagonists of NK1 and NK 2 receptors, respectively. These results suggest that intestinal fluid accu mulation and motility are inhibited by endogenous cannabinoid(s) acting at the cannabinoid CB1 receptors. This effect may be mediated by mechanisms in volving muscarinic cholinoceptors.