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

Authors


Department of Experimental Pharmacology, University of Naples “Federico II”, via D. Montesano 49, 80131 Naples Italy. E-mail: aaizzo@unina.it

Institute for the Chemistry of Molecules of Biological Interest, National Research Council, via Toiano 6, 80072, Arco Felice (NA), Italy. E-mail: vdimarzo@icmib.na.cnr.it

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 CB1 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 CB1 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’ CB1 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

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