TY - JOUR
T1 - Cannabinoid CB 1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation
AU - Izzo, Angelo A.
AU - Fezza, Filomena
AU - Capasso, Raffaele
AU - Bisogno, Tiziana
AU - Pinto, Luisa
AU - Iuvone, Teresa
AU - Esposito, Giuseppe
AU - Mascolo, Nicola
AU - Di Marzo, Vincenzo
AU - Capasso, Francesco
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - 2-arachidonylglycerol
KW - Anandamide
KW - Cannabinoid receptors
KW - Endocannabinoids
KW - Inflammatory bowel disease
KW - Intestinal motility
KW - Intestine
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M3 - Article
C2 - 11588110
AN - SCOPUS:0034740564
VL - 134
SP - 563
EP - 570
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 3
ER -