Rapid effects of aldosterone on sodium-hydrogen exchange in isolated colonic crypts.
Rapid effects of aldosterone on sodium-hydrogen exchange in isolated colonic crypts.
复制标题
醛固酮对离体结肠隐窝中钠-氢交换的快速影响。
DOI：
10.1007/s002329900534
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Geibel,JP
中科院分区：
文献类型：
--
作者：
Winter,DC;Schneider,MF;O'Sullivan,GC;Harvey,BJ;Geibel,JP
醛固酮通过刺激跨上皮电解质转运，在细胞外液容量的动态平衡调节中发挥核心作用。这些效应包括与细胞内受体的结合、基因组事件的修饰和蛋白质的合成。在各种非上皮性组织中观察到细胞对类固醇激素的快速反应。由于这些快速的类固醇反应不受蛋白质合成抑制剂的影响，所以人们提出了“非基因组”这一术语。我们假设最近被证明吸收液体的结肠隐窝对醛固酮反应迅速。用共聚焦激光成像技术记录了装载了pH敏感的荧光染料(BCECF)的隐窝的细胞质pH变化。乙基异丙基阿米洛利或无细胞外钠可抑制醛固酮作用一分钟内结肠隐窝细胞内碱化，但不受蛋白质合成抑制剂的影响。这种快速而独特的类固醇作用的起源涉及一条信号转导途径，涉及G蛋白、蛋白激酶C和前列腺素。通过实时成像，我们已经证实，醛固酮上调了结肠隐窝中的钠氢交换，这种上调不依赖于传统的受体。醛固酮对上皮细胞离子转运的这种明显的、快速的作用对于我们理解健康和疾病中的液体和电解质的动态平衡具有重要的意义。
Aldosterone plays a central role in the homeostatic regulation of extracellular fluid volume by stimulating transepithelial electrolyte transport. These effects involve binding to an intracellular receptor, modification of genomic events and protein synthesis. Rapid cellular responses to steroid hormones have been observed in a variety of nonepithelial tissues. The term ``nongenomic'' has been proposed for these fast steroid responses since they are unaffected by inhibitors of protein synthesis. We hypothesized that colonic crypts, recently demonstrated to absorb fluid, would respond rapidly to aldosterone.Cytoplasmic pH changes in crypts loaded with a pH-sensitive, fluorescent dye (BCECF) were recorded with confocal laser imaging. An intracellular alkalization of colonic crypts was observed within one minute of aldosterone application that was inhibited by ethylisopropylamiloride or the absence of extracellular sodium, yet unaffected by inhibitors of protein synthesis. The genesis of this rapid and distinct steroid action involves a signal transduction pathway that involves G proteins, protein kinase C, and prostaglandins.We have identified, by real-time imaging, a nongenomic upregulation of sodium-hydrogen exchange in colonic crypts by aldosterone that occurs independent of the traditional receptor. This distinct, rapid onset effect of aldosterone on epithelial ion transport has major implications for our understanding of fluid and electrolyte homeostasis in health and disease.