Rokaw M D, Benos D J, Palevsky P M, Cunningham S A, West M E, Johnson J P
Laboratory of Epithelial Cell Biology, Renal-Electrolyte Division, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
J Biol Chem. 1996 Feb 23;271(8):4491-6. doi: 10.1074/jbc.271.8.4491.
The action of aldosterone to increase apical membrane permeability in responsive epithelia is thought to be due to activation of sodium channels. This channel is regulated, in part, by G-proteins, but it is not known if this mechanism is regulated by aldosterone. We report that aldosterone stimulates the expression of the 41-kDa alphai3 subunit of the heterotrimeric GTP-binding proteins in A-6 cells. Both mRNA and the total amount of this protein are increased by aldosterone. The G-protein is palmitoylated in response to the steroid, and the newly synthesized subunit is found to co-localize with the sodium channel. Aldosterone stimulation of sodium transport is significantly inhibited by inhibition of palmitoylation. These results suggest that aldosterone regulates sodium channel activity in epithelia through stimulation of the expression and post-translational targeting of a channel regulatory G-protein subunit.
醛固酮在反应性上皮细胞中增加顶端膜通透性的作用被认为是由于钠通道的激活。该通道部分受G蛋白调节，但尚不清楚这种机制是否受醛固酮调节。我们报告醛固酮刺激A-6细胞中异三聚体GTP结合蛋白的41-kDa alphai3亚基的表达。醛固酮可增加该蛋白的mRNA和总量。该G蛋白响应类固醇而发生棕榈酰化，并且发现新合成的亚基与钠通道共定位。棕榈酰化的抑制显著抑制了醛固酮对钠转运的刺激。这些结果表明，醛固酮通过刺激通道调节性G蛋白亚基的表达和翻译后靶向作用来调节上皮细胞中的钠通道活性。
