Cannabinoid CB 1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation

Angelo A. Izzo, Filomena Fezza, Raffaele Capasso, Tiziana Bisogno, Luisa Pinto, Teresa Iuvone, Giuseppe Esposito, Nicola Mascolo, Vincenzo Di Marzo, Francesco Capasso

Research output: Contribution to journalArticlepeer-review

Abstract

1. 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. 2. 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 3. 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. 4. 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. 5. 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.

Original languageEnglish
Pages (from-to)563-570
Number of pages8
JournalBritish Journal of Pharmacology
Volume134
Issue number3
Publication statusPublished - 2001

Keywords

  • 2-arachidonylglycerol
  • Anandamide
  • Cannabinoid receptors
  • Endocannabinoids
  • Inflammatory bowel disease
  • Intestinal motility
  • Intestine

ASJC Scopus subject areas

  • Pharmacology

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