Cannabinoid CB1-receptor Mediated Regulation of Gastrointestinal Motility in Mice in a Model of Intestinal Inflammation

Br J Pharmacol. 2001 Oct;134(3):563-70. doi: 10.1038/sj.bjp.0704293.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Animals
  • Cannabinoid Receptor Modulators
  • Cannabinoids / agonists
  • Cannabinoids / metabolism*
  • Cannabinol / pharmacology
  • Cannabinol / therapeutic use
  • Croton Oil
  • Cyclohexanols / pharmacology
  • Cyclohexanols / therapeutic use
  • Dermatologic Agents
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Gastrointestinal Motility / drug effects
  • Gastrointestinal Motility / physiology*
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / physiopathology*
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Male
  • Mice
  • Mice, Inbred ICR
  • Piperidines / pharmacology
  • Pyrazoles / pharmacology
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors
  • Receptors, Drug / biosynthesis
  • Receptors, Drug / physiology*
  • Rimonabant

Substances

  • Analgesics
  • Cannabinoid Receptor Modulators
  • Cannabinoids
  • Cyclohexanols
  • Dermatologic Agents
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Cannabinol
  • Croton Oil
  • 3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
  • Rimonabant