Barthó L, Lefebvre R A
Department of Pharmacology, University Medical School Pécs, Hungary.
Arch Int Pharmacodyn Ther. 1995 Jan-Feb;329(1):53-66.
Nitric oxide (NO) seems to be involved as neurotransmitter in nonadrenergic noncholinergic (NANC) smooth muscle relaxation throughout the gastrointestinal tract. Contractile responses to NO in the gastrointestinal smooth muscle have also been reported. In the guinea-pig ileal longitudinal muscle-myenteric plexus preparation at basal tone, NO induces a moderate relaxation followed by an aftercontraction; the latter is blocked by tetrodotoxin. The aftercontraction is also reduced by atropine, the remaining part being inhibited by a substance P antagonist. This indicates the activation of cholinergic and, possibly, tachykininergic neurons; it is not clear whether this represents a rebound phenomenon to the relaxation or a direct action of NO, initially masked by the relaxation. Nitrergic "off"-contractions, in response to electrical stimulation of the inhibitory NANC nerves, were reported in the opossum esophageal body and in the cat distal colon. Primary contractions to NO have been reported in the rat ileum and in the longitudinal muscle of the opossum esophagus. In the rat preparation, the contraction to NO is observed at lower concentrations than the relaxant effect. While the contraction in the opossum seems to be related to guanylate cyclase activation, this is not the case in the rat ileum, as methylene blue did not influence the contractions and 8-bromo-cGMP only had a relaxant effect. No clear-cut rise in cGMP was observed during the NO-induced contraction. The NO-induced contraction was also not influenced by ryanodine but it was concentration-dependently reduced by nifedipine, suggesting that it is related to extracellular calcium influx through L-type calcium channels. Primary contractions due to NO were also observed in the rat whole ileum and in the rat caecal longitudinal muscle, while aftercontractions, due to NO, were also obtained in the rat descending, transverse and sigmoid colon, as well as in the cat ileal longitudinal muscle.
一氧化氮（NO）似乎作为神经递质参与胃肠道非肾上腺素能非胆碱能（NANC）平滑肌的舒张。胃肠道平滑肌对NO的收缩反应也有报道。在基础张力下的豚鼠回肠纵肌 - 肠肌丛标本中，NO诱导适度舒张，随后出现后收缩；后者被河豚毒素阻断。阿托品也可减少后收缩，剩余部分被P物质拮抗剂抑制。这表明胆碱能神经元以及可能的速激肽能神经元被激活；尚不清楚这是对舒张的反弹现象还是NO的直接作用，最初被舒张所掩盖。在负鼠食管体和猫远端结肠中，有报道称对抑制性NANC神经进行电刺激会引发硝能“关闭”收缩。在大鼠回肠和负鼠食管纵肌中已报道了对NO的原发性收缩。在大鼠标本中，观察到对NO的收缩浓度低于舒张效应的浓度。虽然负鼠中的收缩似乎与鸟苷酸环化酶激活有关，但在大鼠回肠中并非如此，因为亚甲蓝不影响收缩，而8 - 溴 - cGMP仅具有舒张作用。在NO诱导的收缩过程中未观察到cGMP明显升高。NO诱导的收缩也不受ryanodine影响，但硝苯地平可使其浓度依赖性降低，这表明它与通过L型钙通道的细胞外钙内流有关。在大鼠全回肠和大鼠盲肠纵肌中也观察到了由NO引起的原发性收缩，而在大鼠降结肠、横结肠和乙状结肠以及猫回肠纵肌中也获得了由NO引起的后收缩。
