Cytoprotection by inhibition of chloride channels: the mechanism of action of glycine and strychnine.
Cytoprotection by inhibition of chloride channels: the mechanism of action of glycine and strychnine.
复制标题
通过抑制氯通道进行细胞保护：甘氨酸和士的宁的作用机制。
DOI：
10.1016/0024-3205(93)90539-f
复制
发表时间：
1993
期刊：
影响因子：
6.1
通讯作者：
Schnellmann,RG
中科院分区：
文献类型：
--
作者：
Miller,GW;Schnellmann,RG
先前的研究表明，士的宁模仿甘氨酸的细胞保护作用 (1)，并且士的宁在细胞保护浓度下与肾近端小管 (RPT) 特异性结合 (2)。本研究的目的是确定士的宁和甘氨酸的细胞保护作用机制。抗霉素 A (0.1 μM) 在线粒体抑制之后、乳酸脱氢酶 (LDH) 活性（细胞死亡/裂解的标志物）释放之前引起氯离子流入。添加马钱子碱或甘氨酸可防止氯离子流入和 LDH 释放。氯离子通道抑制剂依他尼酸、呋塞米、蒽9-甲酸、DIDS和SITS降低了暴露于抗霉素A的RPT中LDH的释放，其效力顺序为DIDS>依他尼酸=呋塞米=蒽-9-羧酸>SITS。这些数据与前面的论文相结合，表明氯离子流入在细胞死亡/裂解中发挥着关键作用；支持 RPT 质膜上存在一个新的士的宁结合位点，该位点与氯离子通道偶联；并表明甘氨酸和马钱子碱通过抑制氯离子流入而具有细胞保护作用。
Previous studies have demonstrated that strychnine mimics the cytoprotective effects of glycine (1) and that strychnine binds specifically to renal proximal tubules (RPT) at cytoprotective concentrations (2). The goal of this study was to determine a mechanism by which strychnine and glycine are cytoprotective. Antimycin A (0.1 μM) caused chloride influx subsequent to mitochondrial inhibition and prior to the release of lactate dehydrogenase (LDH) activity (a marker of cell death/lysis). The addition of strychnine or glycine prevented the chloride influx and LDH release. The chloride channel inhibitors ethacrynic acid, furosemide, anthracene-9-carboxylic acid, DIDS, and SITS decreased LDH release in RPT exposed to antimycin A with a rank order of potency of DIDS > ethacrynic acid=furosemide=anthracene-9-carboxylic acid > SITS. These data, in conjuction with the preceeding paper, indicate a critical role for chloride influx in cell death/lysis; support the existence of a novel strychnine binding site on the plasma membrane of RPT that is coupled to a chloride channel; and suggest that glycine and strychnine are cytoprotective through their inhibition of chloride influx.