Aldosterone stimulates activity and surface expression of NHE3 in human primary renal proximal tubule epithelial cells (RPTEC)

Karina Drumm, Theresia R. Kress, Birgit Gassner, Alexander W. Krug, Michael Gekle

Research output: Contribution to journalArticle

Abstract

The steroid hormone aldosterone is a major regulator of extracellular volume and blood pressure. Aldosterone effectors are for example the epithelial Na + channel (ENaC), the Na +-K +-ATPaSe and the proximal tubule Na +/H + exchanger isoform 3 (NHE3). The aim of this study was to investigate whether aldosterone acts directly on proximal tubule cells to stimulate NHE3 and if so whether the EGF-receptor (EGFR) is involved. For this purpose, primary human renal proximal tubule cells were exposed to aldosterone. NHE3 activity was determined from Na +- dependent pH-recovery, NHE3 surface expression was determined by biotinylation and immunoblotting. EGFR-expression was assessed by ELISA. pH i-measurements revealed an aldosterone-induced increase in NHE3 activity, which was inhibited by the mineralocorticoid receptor blocker spironolactone and by the EGFR-kinase inhibitor AG1478. Immunoprecipitation and immunoblot analysis showed an aldosterone-induced increase in NHE3 surface expression, which was also inhibited by spironolactone and AG1478. Furthermore, aldosterone enhanced EGFR-expression. In conclusion, aldosterone stimulates NHE3 in human proximal tubule cells. The underlying mechanisms include AG1478 inhibitable kinase and are paralleled by enhanced EGFR expression, which could be compatible with EGF-receptor-pathway-dependent surface expression and activity of NHE3 in human primary renal proximal tubule epithelial cells.

Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalCellular Physiology and Biochemistry
Volume17
Issue number1-2
DOIs
Publication statusPublished - 2006

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Keywords

  • Aldosterone
  • EGF-receptor
  • NHE3
  • Proximal tubule epithelial cells

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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