Reaction of nitric oxide with superoxide inhibits basolateral K+ channels in the rat CCD.

Reaction of nitric oxide with superoxide inhibits basolateral K+ channels in the rat CCD.
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一氧化氮与超氧化物的反应抑制大鼠 CCD 中的基底外侧 K 通道。

DOI:
10.1152/ajpcell.1998.275.1.c309
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发表时间:
1998
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
Wang,WH
Wang,WH
中科院分区:
--
文献类型:
--
作者:
Lu,M;Wang,WH

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我们先前证实,一氧化氮(NO)通过cGMP依赖的途径兴奋基底外侧小电导钾通道(SK)[M.Lu和WangW.H.Am]。J.Physiol.270(细胞生理学。39):C1336-C1342,1996]。因为已经证明在高浓度下NO与超氧化物()反应生成过氧亚硝酸盐(Oono−)[W.A.Pryor和G.L.Squirito.Am.J.Physiol.268(肺细胞。摩尔。物理。12):L699-L722,1995和M.S.Wolin.微循环3:1-17,1996],我们利用膜片钳技术进一步研究了高浓度NO对大鼠肾脏皮质集合管SK的影响。加入NO供体[10 0~2 0 0μMS-亚硝基-N-乙酰青霉胺(SNAP)或硝普钠(SNP)]后,通道活性(通道数目与开放概率的乘积)分别降至控制值的15%和2 5%。在胞内清除剂10 mM TIron存在下,NO的抑制作用被完全消除。在对照条件下刺激通道活动的供体10μM SNAP或SNP,在雄激素、邻苯三酚或超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸存在下,也能抑制SK。在外源cGMP存在的情况下,NO的抑制作用仍然存在,提示NO诱导的抑制不是cGMP产生减少的结果。我们的结论是,NO对通道活动的抑制作用是NO和的相互作用的结果。
We previously demonstrated that nitric oxide (NO) stimulates the basolateral small-conductance K+channel (SK) via a cGMP-dependent pathway [M. Lu and W. H. Wang.Am. J. Physiol. 270 (Cell Physiol. 39): C1336–C1342, 1996]. Because NO at high concentration has been shown to react with superoxide () to form peroxynitrite (OONO−) [W. A. Pryor and G. L. Squadrito.Am. J. Physiol. 268 (Lung Cell. Mol. Physiol. 12): L699–L722, 1995 and M. S. Wolin.Microcirculation3: 1–17, 1996], we extended our study to examine, using patch-clamp technique, the effect of high concentrations of NO on SK in cortical collecting duct (CCD) of rat kidney. Addition of NO donors [100–200 μMS-nitroso-N-acetyl-penicillamine (SNAP) or sodium nitroprusside (SNP)] reduced channel activity, defined as the product of channel number and open probability, to 15 and 25% of the control value, respectively. The inhibitory effect of NO was completely abolished in the presence of 10 mM Tiron, an intracellular scavenger of. NO donors, 10 μM SNAP or SNP, which stimulate channel activity under control conditions, can also inhibit SK in the presence of andonor, pyrogallol, or in the presence of an inhibitor of superoxide dismutase, diethyldithiocarbamic acid. The inhibitory effect of NO is still observed in the presence of exogenous cGMP, suggesting that the NO-induced inhibition is not the result of decreased cGMP production. We conclude that the inhibitory effect of NO on channel activity results from an interaction between NO and.
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