1 We have studied the eect of cannabinoid agonists (CP 55,940 and cannabinol) on intestinal motility in a model of intestinal in¯ammation (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
71) and cannabinol (10 ± 3000 nmol mouse 71 ) were more active in delaying intestinal motility in croton oil-treated mice than in control mice. These inhibitory eects were counteracted by the selective cannabinoid CB 1 receptor antagonist SR141716A (16 nmol mouse
71). SR141716A (1 ± 300 nmol mouse 71 ), administered alone, increased intestinal motility to the same extent in both control and croton oil-treated mice 3 Croton oil-induced intestinal in¯ammation was associated with an increased expression of CB 1 receptor, an unprecedented example of up-regulation of cannabinoid receptors during in¯ammation. 4 High levels of anandamide and 2-arachidonylglycerol were detected in the small intestine, although no dierences were observed between control and croton oil-treated mice; by contrast anandamide amidohydrolase activity increased 2 fold in the in¯amed small intestine. 5 It is concluded that in¯ammation 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 in¯amed gut, might tonically inhibit intestinal motility.
, i.p.) but not by SR144528 (52 nmol mouse 71 , i.p.) both in control and croton-oil treated mice. 5 Ganglionic blockade with hexamethonium (69 nmol mouse 71 , i.p.) did not modify the inhibitory eect of i.p.-injected cannabinoid agonists either in control or in croton-oil treated mice. 6 The lower ED 50 values of cannabinoid drugs after i.c.v. administration suggest a central (CB 1 ) site of action. However, a peripheral site of action is suggested by the lack of eect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the eect of cannabinoid agonists by a peripheral mechanism.
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