Nongenomic regulation by aldosterone of the epithelial NHE3 Na +/H+ exchanger

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Abstract

The relevance of nongenomic pathways to regulation of epithelial function by aldosterone is poorly understood. Recently, we demonstrated that aldosterone inhibits transepithelial HCO3- absorption in the renal medullary thick ascending limb (MTAL) through a nongenomic pathway. Here, we examined the transport mechanism(s) responsible for this regulation, focusing on Na+/H+ exchangers (NHE). In the MTAL, apical NHE3 mediates H+ secretion necessary for HCO3- absorption; basolateral NHE1 influences HCO3- absorption by regulating apical NHE3 activity. In microperfused rat MTALs, the addition of 1 nM aldosterone rapidly decreased HCO3- absorption by 30%. This inhibition was unaffected by three maneuvers that inhibit basolateral Na+/H+ exchange and was preserved in MTALs from NHE1 knockout mice, ruling out the involvement of NHE1. In contrast, exposure to aldosterone for 15 min caused a 30% decrease in apical Na+/H + exchange activity over the intracellular pH range from 6.5 to 7.7, due to a decrease in Vmax. Inhibition of HCO3- absorption by aldosterone was not affected by 0.1 mM lumen Zn2+ or 1 mM lumen DIDS, arguing against the involvement of an apical H+ conductance or apical K+-HCO3- cotransport. These results demonstrate that aldosterone inhibits HCO3- absorption in the MTAL through inhibition of apical NHE3, and identify NHE3 as a target for nongenomic regulation by aldosterone. Aldosterone may influence a broad range of epithelial transport functions important for extracellular fluid volume and acid-base homeostasis through direct regulation of this exchanger.

Original languageEnglish (US)
Pages (from-to)C757-C763
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number3
DOIs
StatePublished - Mar 1 2006

Keywords

  • Acid-base transport
  • Epithelial Na transport
  • Kidney
  • Thick ascending limb

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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