{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:27:58Z","timestamp":1773408478883,"version":"3.50.1"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,11,1]]},"abstract":"<jats:p> The mineralocorticoid aldosterone is the most important hormone for the regulation of Na<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> homeostasis in mammals and is thereby involved in the regulation of extracellular volume and blood pressure. Because aldosterone is a steroid hormone, the classical way of action involves transcription, translation, and protein synthesis. We previously reported a rapid, nongenomic, and Zn<jats:sup>2+<\/jats:sup>-sensitive action of aldosterone on Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchange in renal epithelial [Madin-Darby canine kidney (MDCK)] cells (M. Gekle, N. Golenhofen, H. Oberleithner, and S. Silbernagl. Proc. Natl. Acad. Sci. 93: 10500\u201310504, 1996). Here we show that, in the absence of Na<jats:sup>+<\/jats:sup> (i.e., with inactive Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchange), aldosterone induces a membrane potential-dependent and Zn<jats:sup>2+<\/jats:sup>-sensitive cytoplasmic acidification in MDCK cells within 2\u20134 min. This aldosterone-induced activation of a proton conductance is insensitive to the inhibitor of the classical genomic pathway, spironolactone. Furthermore, the inhibitor of serine\/threonine kinases and staurosporine, as well as the specific inhibitor of protein kinase C (PKC), calphostin C, prevented proton conductance activation. Activation of PKC by phorbol esters mimicked the effect of aldosterone. Furthermore, preincubation of the cells with pertussis toxin reduced the effect of aldosterone significantly. We propose a new nongenomic mechanism of action for aldosterone, independently of the intracellular type 1 mineralocorticoid receptor: G protein-dependent stimulation of PKC by aldosterone leads to the activation of a plasma membrane proton conductance that enhances the activity of Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup>exchange. This rapid nongenomic effect could explain the observation that aldosterone may alter renal Na<jats:sup>+<\/jats:sup> and K<jats:sup>+<\/jats:sup> excretion within 5\u201310 min. <\/jats:p>","DOI":"10.1152\/ajpcell.1997.273.5.c1673","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:14:53Z","timestamp":1514135693000},"page":"C1673-C1678","source":"Crossref","is-referenced-by-count":52,"title":["The mineralocorticoid aldosterone activates  a proton conductance in cultured kidney cells"],"prefix":"10.1152","volume":"273","author":[{"given":"Michael","family":"Gekle","sequence":"first","affiliation":[{"name":"Department of Physiology, University of W\u00fcrzburg, 97070 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Silbernagl","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of W\u00fcrzburg, 97070 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Oberleithner","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of W\u00fcrzburg, 97070 W\u00fcrzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02191908"},{"key":"B3","first-page":"1452","volume":"77","author":"Christ M.","year":"1993","journal-title":"J. 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