The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.

中文翻译：

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肾脏中的水通道蛋白：从分子到药物。

水通道蛋白1（AQP1）的发现回答了长期存在的生物物理问题，即水如何专门穿过生物膜。在肾脏中，至少七个水通道蛋白在不同部位表达。AQP1在近端小管和下肢细小分支中极为丰富，对尿液浓缩至关重要。AQP2仅在连接小管和收集管的主要细胞中表达，是主要的加压素调节水通道。AQP3和AQP4都存在于收集管主细胞的基底外侧质膜中，代表了通过AQP2再次吸收水的出口通道。对患者和转基因小鼠的研究表明，AQP2和AQP3对尿液浓度都是必不可少的。肾脏中还存在另外三种水通道蛋白。AQP6存在于收集导管插层细胞的细胞内小泡中，而AQP8以低丰度存在于近端小管和收集导管主要细胞的细胞内，但是这两个通道的生理功能仍然不确定。AQP7在近端小管细胞的刷状边界丰富，并且可能参与近端小管水的重吸收。血管加压素对人体水分平衡具有严格的调节作用，现在的多项研究都强调了AQP2在其中的重要作用。血管加压素通过将AQP2从细胞内囊泡转运到顶质膜来急性调节肾脏收集管的透水性。人体水分平衡的长期适应性变化部分地由AQP2和AQP3表达水平的调节变化控制。在尿崩症的主要形式中发现缺乏功能性AQP2，在与尿液浓缩缺陷有关的几种疾病中发现表达和靶向性降低，例如获得性肾原性尿崩症，阻塞性多尿以及急性和慢性肾衰竭。相反，在具有水retention留的情况下，例如严重的充血性心力衰竭，妊娠和抗利尿激素分泌不适当的综合征，AQP2表达水平和根尖质膜定位均增加，这暗示了AQP2在水retention留发展中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。在与尿液浓缩缺陷有关的几种疾病中，例如获得性肾原性尿崩症，阻塞性多尿症以及急性和慢性肾衰竭，都可以发现这种蛋白的表达水平降低，表达降低和靶向降低。相反，在具有水retention留的情况下，例如严重的充血性心力衰竭，妊娠和抗利尿激素分泌不适当的综合征，AQP2表达水平和根尖质膜定位均增加，这暗示了AQP2在水retention留发展中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。在与尿液浓缩缺陷有关的几种疾病中，例如获得性肾原性尿崩症，阻塞性多尿症以及急性和慢性肾衰竭，都可以发现这种蛋白的表达水平降低，表达降低和靶向降低。相反，在具有水retention留的情况下，例如严重的充血性心力衰竭，妊娠和抗利尿激素分泌不适当的综合征，AQP2表达水平和根尖质膜定位均增加，这暗示了AQP2在水retention留发展中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。梗阻后多尿，以及急慢性肾功能衰竭。相反，在具有水retention留的情况下，例如严重的充血性心力衰竭，妊娠和抗利尿激素分泌不适当的综合征，AQP2表达水平和根尖质膜定位均增加，这暗示了AQP2在水retention留发展中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。梗阻后多尿，以及急慢性肾功能衰竭。相反，在具有水retention留的情况下，例如严重的充血性心力衰竭，妊娠和抗利尿激素分泌不适当的综合征，AQP2表达水平和根尖质膜定位均增加，这暗示了AQP2在水retention留发展中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。提示AQP2在保水作用中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。提示AQP2在保水作用中的作用。水通道蛋白的持续分析为水平衡和水平衡失调的基本生理学和病理生理学提供了详细的分子见解。