Pech Vladimír, Zheng Wencui, Pham Truyen D, Verlander Jill W, Wall Susan M
Emory University School of Medicine, Renal Division, 1639 Pierce Drive, NE, WMB Room 338, Atlanta, GA 30322, USA.
J Am Soc Nephrol. 2008 Jan;19(1):84-91. doi: 10.1681/ASN.2007030277.
We reported previously that angiotensin II (AngII) increases net Cl(-) absorption in mouse cortical collecting duct (CCD) by transcellular transport across type B intercalated cells (IC) via an H(+)-ATPase-and pendrin-dependent mechanism. Because intracellular trafficking regulates both pendrin and H(+)-ATPase, we hypothesized that AngII induces the subcellular redistribution of one or both of these exchangers. To answer this question, CCD from furosemide-treated mice were perfused in vitro, and the subcellular distributions of pendrin and the H(+)-ATPase were quantified using immunogold cytochemistry and morphometric analysis. Addition of AngII in vitro did not change the distribution of pendrin or H(+)-ATPase within type B IC but within type A IC increased the ratio of apical plasma membrane to cytoplasmic H(+)-ATPase three-fold. Moreover, CCDs secreted bicarbonate under basal conditions but absorbed bicarbonate in response to AngII. In summary, angiotensin II stimulates H(+) secretion into the lumen, which drives Cl(-) absorption mediated by apical Cl(-)/HCO(3)(-) exchange as well as generates more favorable electrochemical gradient for ENaC-mediated Na(+) absorption.
我们之前报道过，血管紧张素II（AngII）通过H(+)-ATP酶和pendrin依赖性机制，经B型闰细胞（IC）的跨细胞转运增加小鼠皮质集合管（CCD）中的净Cl(-)吸收。由于细胞内运输调节pendrin和H(+)-ATP酶，我们推测AngII会诱导这两种交换体中一种或两种的亚细胞重新分布。为了回答这个问题，对用速尿处理过的小鼠的CCD进行体外灌注，并使用免疫金细胞化学和形态计量分析对pendrin和H(+)-ATP酶的亚细胞分布进行定量。体外添加AngII不会改变B型IC内pendrin或H(+)-ATP酶的分布，但会使A型IC内顶端质膜与细胞质H(+)-ATP酶的比例增加三倍。此外，CCD在基础条件下分泌碳酸氢盐，但在AngII作用下吸收碳酸氢盐。总之血管紧张素II刺激H(+)分泌到管腔中，这驱动了由顶端Cl(-)/HCO(3)(-)交换介导的Cl(-)吸收，并为ENaC介导的Na(+)吸收产生更有利的电化学梯度。
