Meulemans A L, Helsen L F, Schuurkes J A
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Feb;347(2):225-30. doi: 10.1007/BF00169272.
Vagal stimulation of the stomach induces a relaxation mediated via non-adrenergic, non-cholinergic (NANC) nerves. The neurotransmitter which is responsible for this relaxation is still unknown. To determine whether nitric oxide (NO) or a NO related substance mediates this relaxation, an intact guinea-pig stomach was mounted in an organ bath, with electrodes surrounding the vagal nerves. Electrical stimulation of the vagal nerves, in the presence of atropine, induced frequency dependent, tetrodotoxin-(TTX) sensitive relaxations of the stomach quantified as changes in volume. These relaxations were not affected by alpha- or beta-adrenoceptor antagonists or guanethidine. Thus they were evoked by non-adrenergic, non-cholinergic (NANC) inhibitory nerves. The relaxant responses could be inhibited in a concentration-dependent manner by NG-nitro-L-arginine (L-NNA) a substance that inhibits the formation of nitric oxide (NO). Addition of L-arginine, the substrate for NO-synthase, reversed the L-NNA-induced-inhibition of the relaxation. Addition of nitroglycerin (a NO-donor) to a non-stimulated stomach mimicked the relaxations observed after vagal stimulation in a concentration dependent manner. These relaxations were insensitive to TTX. Relaxation of the stomach by vagal stimulation was prevented by an inhibitor of soluble guanylate cyclase, methylene blue, further supporting our conclusions. These data indicate that NO or a substance releasing NO plays an important role in NANC-neurotransmission after vagal stimulation of the guinea-pig stomach.
迷走神经对胃的刺激可诱导一种通过非肾上腺素能、非胆碱能（NANC）神经介导的舒张。负责这种舒张的神经递质尚不清楚。为了确定一氧化氮（NO）或与NO相关的物质是否介导这种舒张，将完整的豚鼠胃安装在器官浴槽中，电极环绕迷走神经。在阿托品存在的情况下，电刺激迷走神经可诱导胃产生频率依赖性、对河豚毒素（TTX）敏感的舒张，以体积变化来量化。这些舒张不受α-或β-肾上腺素能受体拮抗剂或胍乙啶的影响。因此，它们是由非肾上腺素能、非胆碱能（NANC）抑制性神经诱发的。NG-硝基-L-精氨酸（L-NNA）是一种抑制一氧化氮（NO）形成的物质，它可以浓度依赖性方式抑制舒张反应。添加L-精氨酸（NO合酶的底物）可逆转L-NNA诱导的舒张抑制。向未受刺激的胃中添加硝酸甘油（一种NO供体），以浓度依赖性方式模拟了迷走神经刺激后观察到的舒张。这些舒张对TTX不敏感。可溶性鸟苷酸环化酶抑制剂亚甲蓝可阻止迷走神经刺激引起的胃舒张，这进一步支持了我们的结论。这些数据表明，NO或释放NO的物质在豚鼠胃迷走神经刺激后的NANC神经传递中起重要作用。
