Stamler J S
Division of Respiratory Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Curr Top Microbiol Immunol. 1995;196:19-36. doi: 10.1007/978-3-642-79130-7_4.
The reactivity of selected RS-NOs has led to the misconception that these compounds are uniformly unstable under physiological conditions. Moreover, current evidence supports the notion that biological responses elicited by RS-NOs may result from either liberation of nitric oxide or from NO group transfer chemistry involving either NO+ or NO-. Some evidence suggests that such reactions may be enzymatically controlled. The data supporting the potential biological relevance of RS-NOs include: (1) evidence that these compounds form under physiological conditions; (2) their identification in insects, lower mammals, and several human biological systems; and (3) findings that RS-NOs possess a wide range of biological activities, including antimicrobial effects, vasodilation, platelet inhibition, bronchodilation and inhibition of intestinal motility, while being relatively resistant to reactions with O2 and O2- associated with NO. toxicity. It is further noteworthy that biological activity of RS-NO is often not related to the propensity to liberate NO., and these adducts are generally more potent and selective in their action than NO. itself (Stamler et al. 1989; Cooke et al. 1990; Rockett et al. 1991; Jansen et al. 1991; Lipton et al. 1993). The data presented here support the idea that RS-NO may be involved in stabilizing nitric oxide-like bioactivity, in transporting and targeting the NO group to specific (thioregulatory) effector sites, in mitigating the cytotoxic effects of nitric oxide that result from reaction with oxygen species, and may serve to regulate protein function in a posttranslational modification akin, perhaps, to phosphorylation. The recently demonstrated NO group transfer reactions to plasma membrane proteins containing reactive sulfhydryls (Lipton et al. 1993; Stamler 1994) also raises the possibility of signal transduction initiated through more traditional "agonist-receptor" mediated pathways.
某些特定的RS-NOs的反应活性导致了一种误解，即这些化合物在生理条件下普遍不稳定。此外，目前的证据支持这样一种观点，即RS-NOs引发的生物反应可能源于一氧化氮的释放，或者源于涉及NO⁺或NO⁻的NO基团转移化学过程。一些证据表明，此类反应可能受酶控制。支持RS-NOs具有潜在生物学相关性的数据包括：（1）这些化合物在生理条件下形成的证据；（2）在昆虫、低等哺乳动物和几种人类生物系统中的鉴定结果；（3）发现RS-NOs具有广泛的生物活性，包括抗菌作用、血管舒张、血小板抑制、支气管舒张和肠道蠕动抑制，同时相对抵抗与NO相关的O₂和O₂⁻反应的毒性。进一步值得注意的是，RS-NO的生物活性通常与释放NO的倾向无关，并且这些加合物在其作用中通常比NO本身更有效和更具选择性（Stamler等人，1989年；Cooke等人，1990年；Rockett等人，1991年；Jansen等人，1991年；Lipton等人，1993年）。此处呈现的数据支持这样一种观点，即RS-NO可能参与稳定一氧化氮样生物活性，将NO基团运输并靶向特定的（硫调节）效应位点，减轻一氧化氮与氧物种反应产生的细胞毒性作用，并且可能在类似于磷酸化的翻译后修饰中调节蛋白质功能。最近证明的NO基团向含有反应性巯基的质膜蛋白的转移反应（Lipton等人，1993年；Stamler，1994年）也增加了通过更传统的“激动剂 - 受体”介导途径启动信号转导的可能性。
