Hurst R D, Chowdhury R, Clark J B
Department of Neurochemistry, Institute of Neurology, London, England.
J Neurochem. 1996 Sep;67(3):1200-7. doi: 10.1046/j.1471-4159.1996.67031200.x.
Nitric oxide may regulate cellular respiration by competition with oxygen at mitochondrial cytochrome oxidase. Using an astrocyte-derived cell line, we have compared the mechanism of action of the nitric oxide-generating compound Roussin's black salt with that of sodium nitroprusside on cellular oxygen consumption. Intense light exposure induced the release of large quantities of nitric oxide from both of the donor compounds. However, in room light only Roussin's black salt generated low levels of the radical. Simultaneous measurement of oxygen consumption and of nitric oxide production demonstrated that sodium nitroprusside only had inhibitory actions when exposed to intense light (nitric oxide release), whereas Roussin's black salt had inhibitory actions in room light. Extracellular haemoglobin did not prevent the inhibition of respiration rate induced by Roussin's black salt even though stimulation of nitric oxide release on light exposure was markedly reduced. Preincubation of cells with Roussin's black salt and subsequent measurement of levels of light-liberated nitric oxide demonstrated that the compound was rapidly internalised. The uptake of sodium nitroprusside was minimal. These data suggest that, in contrast to sodium nitroprusside, the cellular internalisation of Roussin's black salt allows site-directed nitric oxide release and very effective inhibition of cellular respiration.
一氧化氮可能通过在线粒体细胞色素氧化酶处与氧气竞争来调节细胞呼吸。利用一种星形胶质细胞衍生的细胞系,我们比较了产生一氧化氮的化合物鲁辛黑盐与硝普钠对细胞耗氧量的作用机制。强光照射会导致这两种供体化合物释放大量一氧化氮。然而,在室内光线下,只有鲁辛黑盐会产生低水平的自由基。同时测量耗氧量和一氧化氮产量表明,硝普钠只有在强光照射(一氧化氮释放)时才有抑制作用,而鲁辛黑盐在室内光线下就有抑制作用。细胞外血红蛋白并不能阻止鲁辛黑盐对呼吸速率的抑制,尽管光照刺激下一氧化氮释放的增加明显减少。用鲁辛黑盐对细胞进行预孵育,随后测量光释放的一氧化氮水平,结果表明该化合物能迅速被细胞内化。硝普钠的摄取量极少。这些数据表明,与硝普钠不同,鲁辛黑盐的细胞内化允许一氧化氮在特定部位释放,并能非常有效地抑制细胞呼吸。