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

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.

• Authors: A A Izzo, F Fezza, R Capasso, T Bisogno, L Pinto, T Iuvone, G Esposito, N Mascolo, V Di Marzo, F Capasso
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 134 Issue 3 Pg. 563-70 (Oct 2001) ISSN: 0007-1188 [Print] England
• PMID: 11588110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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