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Selected Publication:
Gekle, M; Freudinger, R; Mildenberger, S; Schenk, K; Marschitz, I; Schramek, H.
Rapid activation of Na+/H+-exchange in MDCK cells by aldosterone involves MAP-kinase ERK1/2.
Pflugers Arch. 2001; 441(6):781-786
Doi: 10.1007/s004240000507
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- Co-authors Med Uni Graz
- Marschitz Ingrid Christine
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- Abstract:
- The mineralocorticoid aldosterone is essential for the adequate regulation of electrolyte homeostasis, extracellular volume and blood pressure. As a steroid hormone it influences cellular functions by genomic actions. Previously it has been shown that aldosterone can activate Na+/H+-exchange (NHE) by a rapid, nongenomic mechanism. Because (1) NHE can be regulated by ERK1/2 (extracellular signal-regulated kinase) and (2) steroids have been reported to rapidly activate ERK1/2, we tested the hypothesis that activation of NHE by aldosterone involves ERK1/2, using MDCK-C11 cells. We show that nanomolar concentrations of aldosterone induce a rapid, non-genomic activation of NHE, which is characterized by an increased affinity for H+ with minor changes in the maximum transport rate. Accordingly, aldosterone led to an increase of cytosolic steady-state pH. The aldosterone-induced activation of NHE was prevented by the two specific inhibitors of ERK1/2 activation, PD 98059 (2.5 x 10(-5) mol/l) and U0126 (10(-5) mol/l). Furthermore, in the presence of U0126 there was no aldosterone-induced increase of steady-state pH. Finally, aldosterone induced a rapid phosphorylation of ERK1/2, indicating its ability to activate ERK1/2. The data presented here support the hypothesis that the rapid activation of NHE by aldosterone at nanomolar concentrations involves ERK1/2. Thus, in certain cell types, the MAPK cascade may represent an additional pathway mediating rapid aldosterone effects.
- Find related publications in this database (using NLM MeSH Indexing)
- Acid-Base Equilibrium - drug effects
- Aldosterone - pharmacology
- Animals - pharmacology
- Cells, Cultured - pharmacology
- Hydrogen-Ion Concentration - pharmacology
- Kidney Tubules, Distal - cytology
- Mitogen-Activated Protein Kinase 1 - metabolism
- Mitogen-Activated Protein Kinase 3 - metabolism
- Mitogen-Activated Protein Kinases - metabolism
- Research Support, Non-U.S. Gov't - metabolism
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- Find related publications in this database (Keywords)
- aldosterone
- ERK1/2
- MAPK
- MDCK cells