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 stimulation 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)methanone) but not its optical isomer WIN 55212-3. The inhibition of secretion induced by WIN 55212-2 was reversed by SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride), 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 diarrhea unresponsive to available therapies.
Tyler
K
K
Oklahoma Foundation for Digestive Research, Basic Science Laboratories, V.A. Medical Center, Research Administration, Rm. 151, 921 N.E. 13th St., Oklahoma City, OK 73104, USA.
Hillard
C J
CJ
Greenwood-Van Meerveld
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D002186:Cannabinoids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism; D000077285:Rimonabant
D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000109:Acetylcholine; D000077285:Rimonabant