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

Citation
Aa. Izzo et al., Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation, BR J PHARM, 134(3), 2001, pp. 563-570
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
0007-1188 → ACNP
Volume
134
Issue
3
Year of publication
2001
Pages
563 - 570
Database
ISI
SICI code
0007-1188(200110)134:3<563:CCMROG>2.0.ZU;2-7
Abstract
1 We have studied the effect of cannabinoid agonists (CP 55,940 and cannabi nol) on intestinal motility in a model of intestinal inflammation (induced by oral croton oil in mice) and measured cannabinoid receptor expression, e ndocannabinoids (anandamide and 2-arachidonylglycerol) and anandamide amido hydrolase 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 mi ce 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 intestina l motility to the same extent in both control and croton oil-treated mice 3 Croton oil-induced intestinal inflammation was associated with an increas ed expression of CB1 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 inc reased 2 fold in the inflamed small intestine. 5 It is concluded that inflammation of the gut increases the potency of can nabinoid agonists possibly by 'up-regulating' CB1 receptor expression; in a ddition, endocannabinoids, whose turnover is increased in inflamed gut, mig ht tonically inhibit intestinal motility.