Verrey François, Summa Vanessa, Heitzmann Dirk, Mordasini David, Vandewalle Alain, Féraille Eric, Zecevic Marija
Institute of Physiology, University of Zurich, Switzerland.
Ann N Y Acad Sci. 2003 Apr;986:554-61. doi: 10.1111/j.1749-6632.2003.tb07253.x.
Aldosterone controls extracellular volume and blood pressure by regulating Na(+) reabsorption across epithelial cells of the aldosterone-sensitive distal nephron (ASDN). This effect is mediated by a coordinate action on the luminal channel ENaC (generally rate limiting) and the basolateral Na,K-ATPase. Long-term effects of aldosterone (starting within 3 to 6 hours and increasing over days) are mediated by the direct and indirect induction of stable elements of the Na(+) transport machinery (e.g., Na,K-ATPase alpha subunit), whereas short-term effects appear to be mediated by the upregulation of short-lived elements of the machinery (e.g., ENaC alpha subunit) and of regulatory proteins, such as the serum- and glucocorticoid-regulated kinase SGK1. We have recently shown that in cortical collecting duct (CCD) from adrenalectomized (ADX) rats, the increase in Na,K-ATPase activity (approximately threefold in 3 h), induced by a single aldosterone injection, can be fully accounted for by the increase in Na,K-ATPase cell-surface expression. Using the model cell line mpkCCD(cl4), we showed that the parallel increase in Na,K-ATPase function [assessed by Na(+) pump current (I(p)) measurements] and cell-surface expression depends on transcription and translation, and that it is not secondary to a change in apical Na(+) influx. As a first approach to address the question whether the aldosterone-induced regulatory protein SGK1 might play a role in mediating Na,K-ATPase translocation, we have used the Xenopus laevis expression system. SGK1 coexpression indeed increased both the Na(+) pump current and the surface expression of pumps containing the rat alpha1 subunits. In summary, aldosterone controls Na(+) reabsorption in the short term not only by regulating the apical cell-surface expression of ENaC but also by coordinately acting on the basolateral cell-surface expression of the Na,K-ATPase. Results obtained in the Xenopus oocyte expression system suggest the possibility that this effect could be mediated in part by the aldosterone-induced kinase SGK1.
醛固酮通过调节醛固酮敏感性远端肾单位（ASDN）上皮细胞对Na⁺的重吸收来控制细胞外液量和血压。这种作用是通过对管腔通道ENaC（通常是限速环节）和基底外侧Na,K-ATP酶的协同作用来介导的。醛固酮的长期作用（在3至6小时内开始并在数天内增强）是由Na⁺转运机制稳定成分（如Na,K-ATP酶α亚基）的直接和间接诱导介导的，而短期作用似乎是由该机制短暂成分（如ENaCα亚基）以及调节蛋白（如血清和糖皮质激素调节激酶SGK1）的上调介导的。我们最近发现，在肾上腺切除（ADX）大鼠的皮质集合管（CCD）中，单次注射醛固酮诱导的Na,K-ATP酶活性增加（3小时内约增加三倍）可完全由Na,K-ATP酶细胞表面表达的增加来解释。使用模型细胞系mpkCCD(cl4)，我们发现Na,K-ATP酶功能的平行增加[通过Na⁺泵电流（I(p)）测量评估]和细胞表面表达依赖于转录和翻译，且并非继发于顶端Na⁺内流的变化。作为解决醛固酮诱导的调节蛋白SGK1是否可能在介导Na,K-ATP酶易位中起作用这一问题的第一步，我们使用了非洲爪蟾表达系统。SGK1共表达确实增加了Na⁺泵电流以及含有大鼠α1亚基的泵的表面表达。总之，醛固酮在短期内控制Na⁺重吸收不仅通过调节ENaC的顶端细胞表面表达，还通过对Na,K-ATP酶的基底外侧细胞表面表达协同起作用。在非洲爪蟾卵母细胞表达系统中获得的结果提示，这种作用可能部分由醛固酮诱导的激酶SGK1介导。
