Cannabinoid CB1‐receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation

Abstract

We have studied the effect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, endocannabinoids (anandamide and 2‐arachidonylglycerol) and anandamide amidohydrolase activity both in physiological and pathophysiological states. CP 55,940 (0.03 – 10 nmol mouse−1) and cannabinol (10 – 3000 nmol mouse−1) were more active in delaying intestinal motility in croton oil‐treated mice than in control mice. These inhibitory effects were counteracted by the selective cannabinoid CB 1 receptor antagonist SR141716A (16 nmol mouse−1). SR141716A (1 – 300 nmol mouse−1), administered alone, increased intestinal motility to the same extent in both control and croton oil‐treated mice Croton oil‐induced intestinal inflammation was associated with an increased expression of CB 1 receptor, an unprecedented example of up‐regulation of cannabinoid receptors during inflammation. High levels of anandamide and 2‐arachidonylglycerol were detected in the small intestine, although no differences were observed between control and croton oil‐treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the inflamed small intestine. It is concluded that inflammation of the gut increases the potency of cannabinoid agonists possibly by ‘up‐regulating’ CB 1 receptor expression; in addition, endocannabinoids, whose turnover is increased in inflamed gut, might tonically inhibit intestinal motility. British Journal of Pharmacology (2001) 134, 563–570; doi:10.1038/sj.bjp.0704293