Español A J, Sales M E
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.
Pharmacol Res. 2000 Nov;42(5):489-93. doi: 10.1006/phrs.2000.0723.
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.
回肠运动的副交感神经激活对肠道生理至关重要。我们之前已经证明，卡巴胆碱可激活大鼠肠道的毒蕈碱型乙酰胆碱受体（mAChR），并通过磷脂酶C刺激回肠运动。这种激活会诱导磷酸肌醇周转和细胞内钙动员。我们在此表明，一氧化氮合酶（NOS）抑制剂N（G）-单甲基精氨酸可增强卡巴胆碱对大鼠回肠蠕动的刺激作用。因此，我们证实卡巴胆碱以剂量依赖的方式增加了一种依赖钙-钙调蛋白结合的NOS同工型的活性。其产物一氧化氮（NO）不仅可激活鸟苷酸环化酶，诱导cGMP合成，还可激活环氧化酶，产生前列腺素E（2）。该前列腺素可能与NO协同作用，诱导回肠平滑肌舒张。
