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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >The Zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic Cl- absorption, via basolateral KCC1, and reduces fluid loss
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The Zn2+-sensing receptor, ZnR/GPR39, upregulates colonocytic Cl- absorption, via basolateral KCC1, and reduces fluid loss

机译：Zn2 + -Sensing受体，ZnR / GPR39，通过基于基石KCC1上调结肠织物色素，并降低流体损失

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Administration of zinc, as a complement to oral rehydration solutions, effectively diminishes duration and severity of diarrhea, but it is not known whether it merely fulfills a nutritional deficiency, or if zinc has a direct role of regulating solute absorption. We show that Zn2+ acts via a specific receptor, ZnR/GPR39, to reduce fluid loss. Intestinal fluid secretion triggered by cholera toxin (CTx) was lower in WI' mice compared to ZnR/GPR39 KO. In the absence of dietary Zn2+ we observed similar fluid accumulation in NT and ZnR/GPR39 KO mice, indicating that Zn2+ and ZnR/GPR39 are both required for a beneficial effect of Zn2+ in diarrhea. In primary colonocytes and in Caco-2 colonocytic cells, activation of ZnR/GPR39 enhanced Cl-transport, a critical factor in diarrhea, by upregulating K+/C1-cotransporter (KCC1) activity. Importantly, we show basolateral expression of KCC1 in mouse and human colonocytes, thus identifying a novel Cl-absorption pathway. Finally, inhibition of KCC-dependent Cltransport enhanced CTx-induced fluid loss. Altogether, our data indicate that Zn2+ acting via ZnR/GPR39 has a direct role in controlling Cl-absorption via upregulation of basolateral KCC1 in the colon. Moreover, colonocytic ZnR/GPR39 and KCC1 reduce water loss during diarrhea and may therefore serve as effective drug targets. (C) 2017 Elsevier B.V. All rights reserved.
机译：锌的施用作为口服补液溶液的补充，有效地减少了腹泻的持续时间和严重程度，但尚不清楚它是否仅满足营养缺乏，或者锌具有调节溶质吸收的直接作用。我们表明Zn2 +通过特定受体ZnR / GPR39作用，以减少流体损失。与ZnR / GPR39 KO相比，Wi'小鼠的霍乱毒素（CTX）触发的肠道流体分泌较低。在没有膳食Zn2 +的情况下，我们观察到NT和ZnR / GPR39 KO小鼠中的类似流体积累，表明Zn2 +和ZnR / GPR39都需要Zn2 +在腹泻中的有益作用。在原代结肠细胞和CaCO-2结肠细胞中，通过上调K + / C1-COTRANSPORTER（KCC1）活性，激活ZnR / GPR39增强Cl-Tranturant，腹泻的关键因素。重要的是，我们展示了小鼠和人性结肠细胞中Kcc1的基底外侧表达，从而鉴定了一种新型Clovaltion途径。最后，抑制KCC依赖性CLTransport的增强CTX诱导的流体损失。完全，我们的数据表明，通过ZnR / GPR39的Zn2 +作用具有直接作用，在通过在结肠中的基底外侧Kcc1的上调来控制Cloging。此外，结肠型ZnR / GPR39和KCC1降低了腹泻期间的水分，因此可以用作有效的药物靶标。 （c）2017 Elsevier B.v.保留所有权利。

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