Rapid actions of aldosterone on cells from renal epithelium: the possible role of EGF-receptor signaling.
It has been suggested that steroids interact with peptide hormones in part by rapid, potentially non-genomic, mechanisms. The peptide hormone epidermal growth factor (EGF) regulates cell proliferation and ion transport using ERK1/2 as downstream signal. Furthermore, the EGF-receptor (EGF-R) is involved in signaling by G-protein-coupled receptors, growth hormone and cytokines via transactivation. We show that aldosterone modulates Na(+)/H(+)-exchange in renal collecting duct-derived Madin-Darby canine kidney (MDCK) cells via ERK1/2 in a similar way as compared to growth factors. Furthermore, we tested the hypothesis that aldosterone uses the EGF-R as heterologous signal transducer in MDCK cells. Aldosterone induces a rapid increase of ERK1/2 phosphorylation and cytosolic Ca(2+)-concentration of similar extend as compared to EGF. Furthermore, aldosterone stimulates EGF-R Tyr-phosphorylation. Inhibition of EGF-R kinase abolished aldosterone-induced signaling. Aldosterone-induced Ca(2+)-influx seems to be mediated by the activation of ERK1/2, whereas ERK1/2 activation does not depend on Ca(2+)-influx. Our data show that aldosterone uses the EGF-R-ERK1/2 signaling cascade to elicit its rapid effects in MDCK cells.
Gekle
Michael
M
Physiologisches Institut, University of Würzburg, Würzburg, Germany. michael.gekle@mail.uni-wuerzburg.de
Freudinger
Ruth
R
Mildenberger
Sigrid
S
Silbernagl
Stefan
S
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D007668:Kidney / Q000166:cytology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism
D017923:Sodium-Hydrogen Exchangers; D000450:Aldosterone; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium