INHIBITION OF INTESTINAL MOTILITY BY ANANDAMIDE, AN ENDOGENOUS CANNABINOID

The endogenous cannabinoid ligand anandamide (arachidonylethanolamide) inhibited the intestinal passage of a charcoal meal when administered s.c. in mice at doses ranging from 0.1 to 50 mg/kg. This effect was p revented by the cannabinoid CB1 receptor antagonist SR141716A dichloro phenyl)-4-methyl-1H-pyrazole-3-carboxamide . HCl] (1 mg/kg s.c.), but it was not affected by the anandamide transport inhibitor, N-(4-hydrox yphenyl) arachidonylethanolamide (AM404) (50 mg/kg, s.c.). The results indicate that anandamide modulates intestinal motility in mice by act ivating cannabinoid CB1 receptors. They also suggest that anandamide t ransport, which was previously shown to participate in terminating neu ral and vascular responses to anandamide, does not contribute to anand amide inactivation in intestinal tissue. (C) 1997 Elsevier Science B.V .