Ouabain modulation of endothelial calcium signaling in descending vasa recta.

Ouabain modulation of endothelial calcium signaling in descending vasa recta.
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哇巴因对直肠降血管内皮钙信号传导的调节。

DOI:
10.1152/ajprenal.00326.2005
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发表时间:
2006
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Pallone,ThomasL
Pallone,ThomasL
中科院分区:
--
文献类型:
--
作者:
Pittner,Janos;Rhinehart,Kristie;Pallone,ThomasL

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使用Fura 2负载的血管,我们测试了哇巴因是否调节大鼠直降血管(DVR)中内皮细胞胞浆钙浓度([Ca 2 +]CYT)。在10 - 10和10 - 4 M之间的广泛范围内,哇巴因引起双相峰和平台[Ca 2 +] CYP升高。硝苯地平阻断电压门控性钙离子进入并不影响哇巴因缓解肌内皮间隙连接作用的反应。用SEA-0400(10− 6 M)降低细胞外Na+浓度([Na+]o)或Na+/Ca 2+交换器(NCX)抑制可升高[Ca 2 +]CYT,支持NCX在基础[Ca 2 +]CYT设置中的作用。SEA-0400可阻断哇巴因诱导的[Ca ~(2+)]-CYP反应,提示NCX是介导剂。哇巴因或[Na+] o还原后[Ca 2 +] CYP升高的瞬时峰相被2-氨基乙氧基二苯基硼酸酯(5 × 10− 5 M)消除。用La 3+(10 μM)或SKF-96365(10 μM)阻断阳离子通道也减弱了哇巴因诱导的[Ca 2 +] CYP反应。哇巴因预处理增加缓激肽(10− 7 M)引起的[Ca 2 +] CYP升高。我们的结论是,哇巴因敏感的Na+-K+-ATP酶的抑制增强DVR内皮细胞的Ca 2+库负荷,并通过涉及NCX、Ca 2+释放和阳离子通道激活的机制调节[Ca 2 +] CYP信号。
Using fura 2-loaded vessels, we tested whether ouabain modulates endothelial cytoplasmic calcium concentration ([Ca2+]CYT) in rat descending vasa recta (DVR). Over a broad range between 10−10and 10−4M, ouabain elicited biphasic peak and plateau [Ca2+]CYTelevations. Blockade of voltage-gated Ca2+entry with nifedipine did not affect the response to ouabain mitigating against a role for myo-endothelial gap junctions. Reduction of extracellular Na+concentration ([Na+]o) or Na+/Ca2+exchanger (NCX) inhibition with SEA-0400 (10−6M) elevated [Ca2+]CYT, supporting a role for NCX in the setting of basal [Ca2+]CYT. SEA-0400 abolished the [Ca2+]CYTresponse to ouabain implicating NCX as a mediator. The transient peak phase of [Ca2+]CYTelevation that followed either ouabain or reduction of [Na+]owas abolished by 2-aminoethoxydiphenyl borate (5 × 10−5M). Cation channel blockade with La3+(10 μM) or SKF-96365 (10 μM) also attenuated the ouabain-induced [Ca2+]CYTresponse. Ouabain pretreatment increased the [Ca2+]CYTelevation elicited by bradykinin (10−7M). We conclude that inhibition of ouabain-sensitive Na+-K+-ATPase enhances DVR endothelial Ca2+store loading and modulates [Ca2+]CYTsignaling through mechanisms that involve NCX, Ca2+release, and cation channel activation.
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