Participation of nitric oxide synthase and cyclo-oxygenase in the signal transduction pathway of ileal muscarinic acetylcholine receptors.
Parasympathetic activation of ileal motility is essential for intestinal physiology. We have previously demonstrated that carbachol activates muscarinic acetylcholine receptors (mAChR) of rat intestine and stimulates ileal motility via phospholipase C. This activation induces phosphoinositide turnover and intracellular calcium mobilization. We show here that carbachol stimulation of rat ileal motility is potentiated by the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl arginine. Thus, we confirm that carbachol increases, in a dose-dependent manner, the activity of a NOS isoform that depends on calcium-calmodulin binding. Its product, nitric oxide (NO), activates not only guanylyl cyclase, inducing cGMP synthesis, but also cyclo-oxygenase, producing prostaglandin E(2). The prostanoid probably cooperates with NO to induce ileal smooth muscle relaxation.
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Departamento de Inmunobiología, Instituto de Oncología Angel H. Roffo, Facultad de Medicina, Universidad de Buenos Aires, Av.San Martín, Buenos Aires, 5481 CP 1417, Argentina.
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007415:Intestinal Obstruction / Q000201:enzymology* / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018679:Cholinergic Agonists; D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D002217:Carbachol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D006152:Cyclic GMP; D015232:Dinoprostone