PGF(2 alpha) regulates the basolateral K channels in the distal convoluted tubule
PGF(2 alpha) regulates the basolateral K channels in the distal convoluted tubule
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PGF(2α) 调节远曲小管的基底外侧 K 通道
DOI：
10.1152/ajprenal.00102.2017
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Wang Wen-Hui
中科院分区：
文献类型：
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作者：
Wang Lijun;Zhang Chengbiao;Su Xiao-Tong;Lin Dao-Hong;Wu Peng;Schwartzman Michal L;Wang Wen-Hui
我们的目的是研究pgf2 α受体（FP）在调节基底外侧40-pS K通道中的作用，pgf2 α受体是远曲小管（DCT）中高表达的前列腺素受体。单通道实验表明，pgf2 α在低浓度（小于500 nM）下对dct中40-pS K通道具有双相作用，而在高浓度（大于1µM）下对40-pS K通道具有抑制作用。此外，13,14-二氢-15-酮-PGF2α（PGF2α的代谢物）和pge2都不能模拟PGF2α对DCT中40-pS K通道的影响。PKC抑制对40-pS K通道无显著影响；而5µM pgf2 α对K通道的抑制作用被消除。此外，PKC刺激可抑制DCT中的40-pS K通道，提示PKC介导了pgf2 α对40-pS K通道的抑制作用。相反，在NADPH氧化酶（NOX）抑制剂DPI处理的DCT中，pgf2 α对40-pS K通道的刺激作用不存在。此外，添加100µM h2o2模拟pgf2 α的刺激作用，增加了DCT中40-pS的K通道活性。此外，500 nM pgf2 α与h2o2的刺激作用不具有相加性，提示pgf2 α对40-pS K通道的刺激作用可能由超氧相关物质介导。Src家族酪氨酸蛋白激酶（SFK）的抑制不仅抑制了DCT中的40-pS K通道，而且完全消除了pgf2 α和h2o2对40-pS K通道的刺激作用。我们得出结论，低剂量的pgf2 α通过NOX-和sfk依赖的机制刺激基底外侧40-pS K通道，而高浓度的pgf2 α通过pkc依赖的途径抑制K通道。
Our aim is to examine the role of PGF2αreceptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF2αhad a biphasic effect on the 40-pS K channel in the DCT–PGF2αstimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 µM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2α(a metabolite of PGF2α) nor PGE2was able to mimic the effect of PGF2αon the 40-pS K channel in the DCT. The inhibition of PKC had no significant effect on the 40-pS K channel; however, it abrogated the inhibitory effect of 5 µM PGF2αon the K channel. Moreover, stimulation of PKC inhibited the 40-pS K channel in the DCT, suggesting that PKC mediates the inhibitory effect of PGF2αon the 40-pS K channel. Conversely, the stimulatory effect of PGF2αon the 40-pS K channel was absent in the DCT treated with DPI, a NADPH oxidase (NOX) inhibitor. Also, adding 100 µM H2O2mimicked the stimulatory effect of PGF2αand increased the 40-pS K channel activity in DCT. Moreover, the stimulatory effect of 500 nM PGF2αand H2O2was not additive, suggesting the role of superoxide-related species in mediating the stimulatory effect of PGF2αon the 40-pS K channel. The inhibition of Src family tyrosine protein kinase (SFK) not only inhibited the 40-pS K channel in the DCT but also completely abolished the stimulatory effects of PGF2αand H2O2on the 40-pS K channel. We conclude that PGF2αat low doses stimulates the basolateral 40-pS K channel by a NOX- and SFK-dependent mechanism, while at high concentrations, it inhibits the K channel by a PKC-dependent pathway.