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 ph ysiology. We have previously demonstrated that carbachol activates muscarin ic acetylcholine receptors (mAChR) of rat intestine and stimulates ileal mo tility via phospholipase C. This activation induces phosphoinositide turnov er and intracellular calcium mobilization. We show here that carbachol stim ulation of rat ileal motility is potentiated by the nitric oxide synthase ( NOS) inhibitor N-G-monomethyl arginine. Thus, we confirm that carbachol inc reases, in a dose-dependent manner, the activity of a NOS isoform that depe nds on calcium-calmodulin binding. Its product, nitric oxide (NO), activate s not only guanylyl cyclase, inducing cGMP synthesis, but also cyclo-oxygen ase, producing prostaglandin E-2. The prostanoid probably cooperates with N O to induce ileal smooth muscle relaxation. (C) 2000 Academic Press.