Inhibition of peristaltic activity by cannabinoids in the isolated distal colon of mouse

The effects of the cannabinoid receptor agonist Win 55,212-2 and of the com petitive cannabinoid receptor antagonist SR 141716A on the electrically-evo ked peristalsis of isolated distal colon of mouse were studied. Intralumina l pressure, longitudinal displacement, ejected fluid volume and changes in morphology of external intestinal wall were simultaneously recorded in the pre-drug period and in presence of Win 55,212-2 alone or in combination wit h SR 141716A, In the pre-drug pe riod (control), peristaltic activity was c haracterised by regular, monophasic waves and the intraluminal content prop elled towards anterograde (oro-aboral) direction with a propulsion velocity of 1.25 +/- 0.1 mm X s(-1). Pressure and shortening waves showed a peak am plitude of 2.43 +/- 0.32 kPa and 1.8 +/- 0.72 mm, respectively. The mean am ount of fluid volume ejected during each contraction was 80 +/- 12.6 mul. T he addition of Win 55,212-2 [10(-7)-10(-4) M] to the organ bath determined a dose-related attenuation of peristaltic activity consequent to the decrea se of circular and longitudinal muscle strength. The decrease of contractil e activity was followed by dose-dependent decrease of the amount of fluid e jected during peristalsis. The effects of Win 55,212-2 [10(-7)-10(-5) M] we re prevented by SR 141716A, indicating the presence of cannabinoid CB1 rece ptors in the mouse distal colon. SR 141716A alone enhanced both tonic and p hasic motor activities in the colonic longitudinal smooth muscle, suggestin g that CB1 receptor antagonists could act either through antagonising the e ffect of endogenous CB1 receptor agonist or by an agonist effect on these r eceptors, The present results further support the hypothesis that cannabino ids perform a neuromodulatory role in various tracts of gastrointestinal sy stem and first demonstrate their action also in the distal colon of rodents . (C) 2001 Elsevier Science Inc. All rights reserved.