Inhibition of small intestinal secretion by cannabinoids is CB1 receptor-mediated in rats

We tested the hypothesis that cannabinoids, acting via a neuronal mechanism of action decrease small intestinal secretion. In vitro electrical stimula tion induced ileal secretion in rats, that was attenuated by a cannabinoid receptor agonist, WIN 55212-2, (mesylate(R)-(+)-[2,3-dihydro-5-methyl-3-[4- morpholino)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthyl)methan one) but not its optical isomer WIN 55212-3. The inhibition of secretion in duced by WIN 55212-2 was reversed by SR141716A (N-(piperidin-1-yl)-5-(4-chl orophenyl)-1(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydroch loride), a cannabinoid CB1 receptor antagonist. An ileal secretory response stimulated by acetylcholine was unaffected by WIN 55212-2. These findings show that cannabinoids inhibit neurally mediated secretion via cannabinoid CB1 receptors. Thus, cannabinoids may have therapeutic potential for diarrh ea unresponsive to available therapies. (C) 2000 Elsevier Science B.V. All rights reserved.