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

Abstract

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 receptor agonist, on acute defaecation and gastrointestinal transit in mice and on intraluminal fluid accumulation in the rat small intestine. SR141716A increased while WIN 55,212-2 decreased defaecation, gastrointestinal transit and 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 gastrointestinal functions studied. The effect of SR141716 on both intestinal fluid accumulation in rats and gastrointestinal transit in mice was inhibited by atropine (1 mg/kg, i.p.), but not by hexamethonium (1 mg/kg, s.c.), SR140333 (20 µg/kg, i.p.) or SR48968 (20 µg/kg, i.p.), antagonists of NK₁ and NK₂ receptors, respectively. These results suggest that intestinal fluid accumulation and motility are inhibited by endogenous cannabinoid(s) acting at the cannabinoid CB₁ receptors. This effect may be mediated by mechanisms involving muscarinic cholinoceptors.