NITROXERGIC NERVES MEDIATE VAGALLY INDUCED RELAXATION IN THE ISOLATED STOMACH OF THE GUINEA-PIG
NITROXERGIC NERVES MEDIATE VAGALLY INDUCED RELAXATION IN THE ISOLATED STOMACH OF THE GUINEA-PIG
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DOI：
10.1073/pnas.88.24.11490
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
VANE, JR
中科院分区：
文献类型：
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作者：
DESAI, KM;ZEMBOWICZ, A;VANE, JR
在豚鼠离体胃中，胆碱能(毒鼠碱)和肾上腺素能阻滞剂刺激迷走神经所引起的松弛是由一氧化氮(NO)介导的。NO合成抑制剂N(G)-单甲基-L-精氨酸对迷走神经松弛的抑制作用证实了这一点。N(G)-单甲基-L-精氨酸可被L-精氨酸部分逆转，但不能与D-精氨酸共同孵育。NO激活可溶性鸟苷环化酶，迷走神经刺激引起的胃松弛可被可溶性鸟苷环化酶抑制剂亚甲蓝所阻断，进一步支持了我们的结论。刺激迷走神经的松弛作用也被神经节烟碱受体的抑制剂六甲溴铵所阻断，从而表明神经节的传递不依赖于神经节前神经元释放的NO。然而，六甲溴铵并不抑制由增加胃内压所引起的胃舒张性，这也是我们先前所描述的由NO所介导的。六甲铵选择性地抑制迷走神经介导的胃松弛，而不是压力诱导的胃松弛，这表明至少存在两条独立的神经通路，能够产生NO，并带来胃对食物或液体的适应。
Here we show that the relaxation induced by stimulation of the vagus nerve in the presence of cholinergic (muscarinic) and adrenergic blockade in the isolated stomach of the guinea pig is mediated by nitric oxide (NO). This is substantiated by inhibition of vagal relaxation by N(G)-monomethyl-L-arginine, an inhibitor of NO synthesis. The effect of N(G)-monomethyl-L-arginine was partially reversed by coincubation with L-arginine but not with D-arginine. NO activates soluble guanylate cyclase, and relaxation of the stomach induced by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. The relaxant effect of vagal stimulation was also ablated by hexamethonium, an inhibitor of ganglionic nicotinic receptors, thereby showing that ganglionic transmission did not rely on NO, through its release from preganglionic neurons. However, hexamethonium did not inhibit the gastric relaxation brought about by increasing the intragastric pressure, which is also mediated by NO as previously described by us. The selective inhibition by hexamethonium of only the vagally mediated relaxation but not of the pressure-induced relaxation of the stomach indicates the existence of at least two separate neuronal pathways able to generate NO and bring about gastric accommodation of food or fluid.