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Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.
- Source :
-
British journal of pharmacology [Br J Pharmacol] 2001 Oct; Vol. 134 (3), pp. 563-70. - Publication Year :
- 2001
-
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.
- Subjects :
- Analgesics pharmacology
Analgesics therapeutic use
Animals
Cannabinoid Receptor Modulators
Cannabinoids agonists
Cannabinol pharmacology
Cannabinol therapeutic use
Croton Oil
Cyclohexanols pharmacology
Cyclohexanols therapeutic use
Dermatologic Agents
Dose-Response Relationship, Drug
Gastrointestinal Motility drug effects
Inflammatory Bowel Diseases chemically induced
Inflammatory Bowel Diseases drug therapy
Inflammatory Bowel Diseases metabolism
Injections, Intraperitoneal
Injections, Intraventricular
Male
Mice
Mice, Inbred ICR
Piperidines pharmacology
Pyrazoles pharmacology
Receptors, Cannabinoid
Receptors, Drug antagonists & inhibitors
Receptors, Drug biosynthesis
Rimonabant
Cannabinoids metabolism
Disease Models, Animal
Gastrointestinal Motility physiology
Inflammatory Bowel Diseases physiopathology
Receptors, Drug physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0007-1188
- Volume :
- 134
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11588110
- Full Text :
- https://doi.org/10.1038/sj.bjp.0704293