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
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.