Angiotensin II stimulates vesicular H+-ATPase in rat proximal tubular cells.
Angiotensin II stimulates vesicular H+-ATPase in rat proximal tubular cells.
复制标题
血管紧张素 II 刺激大鼠近端肾小管细胞中的囊泡 H -ATP 酶。
DOI：
10.1073/pnas.95.16.9665
复制
发表时间：
1998
影响因子：
11.1
通讯作者：
Geibel,JP
中科院分区：
文献类型：
--
作者：
Wagner,CA;Giebisch,G;Lang,F;Geibel,JP
近端小管中介导碳酸氢盐重吸收的H+离子分泌的两种机制已被确定：刷状缘Na/H交换器和生电H+离子分泌。血管紧张素II（AII）已被证明是管腔Na+/H+交换和基底外侧Na+/HCO 3 −共转运蛋白的调节剂。在本研究中，我们研究了AII对H+-ATP酶活性的影响，在离体近端小管片段。H+-ATP酶活性通过监测从浴中除去Na+后的细胞内pH来评估。此外，我们还研究了质子泵抑制剂巴弗洛霉素A1对pH恢复、Cl-去除和秋水仙碱的影响。用pH敏感的荧光染料2′，7′-双（2-羧乙基）-5（6）-羧基荧光素（BCECF）连续测量pH。细胞pH值的恢复观察到外部Na+的情况下，并显着加速AII。AII刺激的pH恢复被巴弗洛霉素A1、清除Cl−、NPPB [5-硝基-2-（3-苯丙胺基）-苯甲酸盐;一种有效的Cl−通道阻断剂]和秋水仙碱完全消除。我们从这些研究中得出结论，AII刺激质子挤出通过H+-ATP酶的Cl−依赖性过程涉及刷状缘插入囊泡。当肾小管暴露于AII时，这一过程可能有助于上调近端小管沿着的HCO 3 −重吸收。
Two mechanisms of H+ion secretion in the proximal tubule that mediate bicarbonate reabsorption have been identified: the brush border Na/H exchanger and electrogenic H+ion secretion. Angiotensin II (AII) has been shown to be a regulator of the luminal Na+/H+exchanger and the basolateral Na+/HCO3−cotransporter. In the present study, we examined the effects of AII on H+-ATPase activity in isolated proximal tubule fragments. H+-ATPase activity was assessed by monitoring intracellular pH after Na+removal from the bath. In addition, we investigated the effects on pH recovery of the proton pump inhibitor bafilomycin A1, removal of Cl−, and of colchicine. pH was continuously measured with the pH-sensitive fluorescent dye 2′, 7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Recovery of cell pH was observed in the absence of external Na+and was significantly accelerated by AII. The AII-stimulated pH recovery was completely abolished by bafilomycin A1, by removal of Cl−, by NPPB [5-nitro-2-(3-phenylpropylamino)-benzoate; a potent Cl−channel blocker], and by colchicine. We conclude from these studies that AII stimulates proton extrusion via H+-ATPase by a Cl−-dependent process involving brush border insertion of vesicles. This process may contribute to up-regulation of HCO3−reabsorption along the proximal tubule when tubules are exposed to AII.