Correia N A, Cavalcanti P M, Oliveira R B, Ballejo G
Departamento de Farmacologia, Universidade de São Paulo, Brasil.
J Auton Pharmacol. 1999 Aug;19(4):233-40. doi: 10.1046/j.1365-2680.1999.00139.x.
Relaxation induced by NANC-nerve stimulation is reduced by nitric oxide synthase (NOS) inhibitors but not by superoxide generators or NO scavengers, casting doubts on the precise nature of the neurotransmitter being released by these nerves. The lack of effect of superoxide anion generators to inhibit nitrergic nerve-mediated relaxations has been attributed to the protective action of high tissue levels of superoxide dismutase (SOD). The effects of hydroquinone, hydroxocobalamin and carboxy-PTIO, three NO inactivators which do not depend on superoxide anion generation, upon nitrergic nerve-mediated relaxations of the rat proximal duodenum were determined in order to elucidate whether they are mediated by free NO. GABA and nicotine caused relaxations of isolated segments of the rat proximal duodenum in a concentration-dependent manner that were abolished by tetrodotoxin (TTX). Similarly, transmural electrical stimulation (TES) caused frequency-dependent relaxations that were also abolished by TTX. The NOS inhibitors L-NAME and L-NOARG reduced in a concentration-dependent manner nerve-mediated relaxations elicited by TES, nicotine and GABA. The effect of NOS inhibitors was prevented by L-arginine but not D-arginine. NO caused concentration-dependent relaxations that were not affected by TTX or L-NOARG but were abolished by hydroquinone, hydroxocobalamin and carboxy-PTIO. In contrast, these compounds failed to affect TES-, nicotine- and GABA-induced relaxations. The lack of effect of hydroquinone, hydroxocobalamin and carboxy-PTIO upon nerve-mediated relaxations was unaltered by pretreatment with the SOD irreversible inhibitor DETCA. The present findings show that nitrergic nerve-mediated relaxations of the rat duodenum are unaffected by NO inactivators that do not generate superoxide anion. It is suggested that either a NO-containing molecule that is unreactive with the inactivators tested is the inhibitory neurotransmitter released by nitrergic nerves or that NOS activity fulfills another role in nitrergic nerves which could be related to the release of an still unidentified transmitter.
一氧化氮合酶（NOS）抑制剂可降低非肾上腺素能非胆碱能（NANC）神经刺激诱导的舒张作用，但超氧化物生成剂或一氧化氮清除剂则无此作用，这使得人们对这些神经释放的神经递质的确切性质产生怀疑。超氧化物阴离子生成剂对抑制氮能神经介导的舒张作用无效，这归因于组织中超氧化物歧化酶（SOD）水平较高的保护作用。为了阐明大鼠近端十二指肠的氮能神经介导的舒张是否由游离一氧化氮介导，我们测定了对苯二酚、羟钴胺素和羧基-PTIO这三种不依赖超氧化物阴离子生成的一氧化氮灭活剂的作用。γ-氨基丁酸（GABA）和尼古丁以浓度依赖的方式引起大鼠近端十二指肠分离段的舒张，这种舒张被河豚毒素（TTX）消除。同样，经壁电刺激（TES）引起频率依赖的舒张，也被TTX消除。NOS抑制剂L-NAME和L-NOARG以浓度依赖的方式降低了TES、尼古丁和GABA引起的神经介导的舒张。L-精氨酸可阻止NOS抑制剂的作用，但D-精氨酸则不能。一氧化氮引起浓度依赖的舒张，不受TTX或L-NOARG影响，但被对苯二酚、羟钴胺素和羧基-PTIO消除。相反，这些化合物未能影响TES、尼古丁和GABA诱导的舒张。用SOD不可逆抑制剂DETCA预处理后，对苯二酚、羟钴胺素和羧基-PTIO对神经介导的舒张作用缺乏影响这一情况未改变。目前的研究结果表明，大鼠十二指肠的氮能神经介导的舒张不受不产生超氧化物阴离子的一氧化氮灭活剂的影响。有人提出，要么是一种与所测试灭活剂无反应的含一氧化氮分子是氮能神经释放的抑制性神经递质，要么是NOS活性在氮能神经中发挥另一种作用，这可能与一种仍未确定的递质的释放有关。
