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首页> 外文期刊>Cellular Physiology and Biochemistry >Pendrin as a Novel Target for Diuretic Therapy
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Pendrin as a Novel Target for Diuretic Therapy

机译：Pendrin作为利尿剂治疗的新靶标

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The Clsup-/sup/HCOsub3/subsup-/sup exchanger pendrin (SLC26A4, PDS) and the thiazide-sensitive NaCl cotransporter NCC (SLC12A3) are expressed on the apical membranes of distal nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na channel (ENaC) and NCC working by itself. Pendrin is expressed on the apical membrane of intercalated cells in late distal convoluted tubule (DCT), connecting tubule (CNT) and the cortical collecting duct (CCD) whereas the thiazide-sensitive NaCl cotransporter NCC is primarily detected on the apical membrane of DCT cells. Recent studies indicate that pendrin expression is increased in kidneys of NCC knockout mice, raising the possibility that pendrin and NCC can compensate for loss of the other by increasing their expression and activity. Current investigations in our laboratories demonstrate that pendrin plays an important role in compensatory salt absorption in response to the loop diuretics and the thiazide derivatives. These studies further demonstrate that whereas single deletion of pendrin or NCC does not cause salt wasting in mutant mice under baseline conditions, double knockout of pendrin and NCC causes profound polyuria and polydipsia, along with salt wasting under basal conditions. As a result, animals develop significant dehydration. We propose that pharmacologic inhibition of pendrin and NCC can provide a novel and strong diuretic regimen for patients with fluid overload, including those with congestive heart failure, nephrotic syndrome or renal failure.
机译：Cl - / HCO 3 -交换体pendrin（SLC26A4，PDS）和噻嗪敏感的NaCl共转运蛋白NCC（SLC12A3）在远端肾单位的顶膜并介导盐的吸收，pendrin与上皮Na通道（ENaC）和NCC共同起作用。 Pendrin在晚期远曲小管（DCT），连接小管（CNT）和皮质收集管（CCD）的插层细胞的顶膜中表达，而对噻嗪类敏感的NaCl共转运蛋白NCC主要在DCT细胞的顶膜上检测到。最近的研究表明，在NCC基因敲除小鼠的肾脏中，pendrin表达增加，这增加了pendrin和NCC可以通过增加它们的表达和活性来补偿彼此损失的可能性。我们实验室中的当前研究表明，响应于di利尿剂和噻嗪衍生物，pendrin在代偿性盐吸收中起着重要作用。这些研究进一步证明，在基线条件下单缺失Pendrin或NCC不会在突变小鼠中造成盐的浪费，而Pendrin和NCC的双重敲除会导致大量的尿和多饮，以及在基础条件下的盐浪费。结果，动物出现了严重的脱水。我们建议药理抑制Pendrin和NCC可以为体液超负荷的患者（包括充血性心力衰竭，肾病综合征或肾衰竭的患者）提供一种新颖而强大的利尿方案。

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