Non-genomic action of the mineralocorticoid aldosterone on cytosolic sodium in cultured kidney cells.
1. The mineralocorticoid aldosterone is essential for the regulation of electrolyte homeostasis, extracellular volume and blood pressure. As a steroid hormone the classical way of action is genomic. Previously we reported a non-genomic action of aldosterone on cytosolic Ca2+ and pH in renal epithelial (MDCK) cells. In parallel, aldosterone induces Zn2+-sensitive cytosolic acidification when extracellular Na+ is absent. 2. We now show that aldosterone (EC50, 7 x 10-11 mol l-1) induces a non-genomic increase in cytosolic sodium in MDCK cells. The membrane-impermeable aldosterone-bovine serum albumin (BSA) conjugate exerted the same effect. The effect of aldosterone was completely abolished by inhibition of Na+-H+ exchange with ethyl-isopropanol amiloride (EIPA). Aldosterone-induced Na+ influx exceeded H+ efflux more than 10-fold. 3. Omission of extracellular Ca2+, inhibition of protein kinase C or pretreatment with pertussis toxin reduced the effect of aldosterone significantly. Zn2+ (IC50, 3.3 x 10-6 mol l-1), but not ouabain, abolished the increase in Na+ almost completely. 4. The aldosterone-induced increase in cytosolic sodium was accompanied by an EIPA- and Zn2+-sensitive cell swelling. 5. Thus, physiological concentrations of aldosterone induce a non-genomic increase in cytosolic sodium concentration by activation of Na+-H+ exchange. Aldosterone exerts its effect, at least in part, at the plasma membrane via interaction with a G-protein-coupled mechanism. 6. The simultaneous activation of the acidification mechanism and Na+-H+ exchange by aldosterone allows a dramatic sodium influx without excessive changes in cytosolic pH and leads to changes in cell volume.
Physiologisches Institut, University of Wurzburg, Wurzburg, Germany. michael.gekle@mail.uni-wuerzburg.de
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Silbernagl
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Wünsch
D000450:Aldosterone / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007668:Kidney; D007700:Kinetics; D008954:Models, Biological; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
D000450:Aldosterone; D010042:Ouabain; D000584:Amiloride; D012964:Sodium; D015032:Zinc; C039614:ethylisopropylamiloride