Ohta H, Bates J N, Lewis S J, Talman W T
Department of Neurology, University of Iowa, Iowa City 52242, USA.
Brain Res. 1997 Jan 23;746(1-2):98-104. doi: 10.1016/s0006-8993(96)01188-2.
Cardiovascular effects elicited by microinjection of L-S-nitrosocysteine in the nucleus tractus solitarii (NTS) were compared and contrasted with those produced by the dextroisomer, other nitric oxide donors and nitric oxide itself. L-S-nitrosocysteine produced dose-related decreases of arterial pressure and heart rate. In contrast, D-S-nitrosocysteine, S-nitrosoglutathione, glyceryl trinitrate, and sodium nitroprusside produced minimal responses that were not dose-related. Likewise, injection of cystine and nitric oxide, two products of S-nitrosocysteine breakdown, produced no significant response. Headspace analysis using chemiluminescence revealed that L- and D-S-nitrosocysteine released identical amounts of nitric oxide when exposed to homogenates of whole rat brain. Responses to L-S-nitrosocysteine were not affected by local injection of oxyhemoglobin or the nitric oxide synthase inhibitor L-nitroarginine methylester. Although injection of L-cysteine into the NTS produced responses similar to those seen with injection of L-S-nitrosocysteine, blockade of excitatory amino acid receptors with kynurenic acid inhibited responses to cysteine but not those to the nitrosothiol. The study demonstrates that S-nitrosocysteine is biologically active in the NTS. Its action is independent of release of nitric oxide from the nitrosothiol but may be mediated through stereoselective sites on target neurons.
将L - S - 亚硝基半胱氨酸微量注射到孤束核(NTS)所引发的心血管效应,与右旋异构体、其他一氧化氮供体及一氧化氮本身所产生的效应进行了比较和对比。L - S - 亚硝基半胱氨酸可引起动脉血压和心率呈剂量相关的下降。相比之下,D - S - 亚硝基半胱氨酸、S - 亚硝基谷胱甘肽、甘油三硝酸酯和硝普钠产生的反应极小,且与剂量无关。同样,注射S - 亚硝基半胱氨酸分解产生的两种产物胱氨酸和一氧化氮,未产生明显反应。利用化学发光进行的顶空分析表明,L - 和D - S - 亚硝基半胱氨酸在暴露于全大鼠脑匀浆时释放出等量的一氧化氮。对L - S - 亚硝基半胱氨酸的反应不受局部注射氧合血红蛋白或一氧化氮合酶抑制剂L - 硝基精氨酸甲酯的影响。虽然将L - 半胱氨酸注射到NTS产生的反应与注射L - S - 亚硝基半胱氨酸时相似,但用犬尿氨酸阻断兴奋性氨基酸受体可抑制对半胱氨酸的反应,却不影响对亚硝基硫醇的反应。该研究表明,S - 亚硝基半胱氨酸在NTS中具有生物活性。其作用独立于亚硝基硫醇释放一氧化氮,但可能通过靶神经元上的立体选择性位点介导。