Chronic metabolic acidosis increases NHE3 protein abundance in rat kidney

Patrice M. Ambühl, Morimasa Amemiya, Monika Danczkay, Marius Lötscher, Brigitte Kaissling, Orson W. Moe, Patricia A. Preisig, Robert J. Alpern

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Chronic metabolic acido-sis increases the activity of the proximal tubule apical membrane Na/H antiporter, which is encoded predominantly by the NHE3 isoform. The present studies examined the effect of chronic metabolic acidosis on apical membrane NHE3 protein abundance in rats. Rats subjected to NH4Cl in their drinking water developed a metabolic acidosis, which decreased in magnitude over 14 days. During this time, renal cortical brush-border membrane NHE3 protein abundance, assessed by Western blot, increased progressively (28% at 3 days, 59% at 7 days, and 90% at 14 days). Immunohistochemistry revealed that the acidosis-induced increase in NHE3 abundance occurred in the apical membranes of the S1 and S2 segments of the proximal tubule and the thick ascending limb. NHE3 mRNA abundance was not significantly increased in these animals, whereas phosphoenol pyruvate carboxykinase and glyceraldehyde-3-phosphate dehydrogenase mRNA abundances were significantly increased. These studies demonstrate that the increase in Na/H antiporter activity seen in metabolic acidosis involves an increase in NHE3 protein abundance, which is distributed along the proximal tubule and the thick ascending limb. In addition, these studies suggest that a component of this adaptation is unrelated to changes in NHE3 mRNA abundance.

Original languageEnglish (US)
Pages (from-to)F917-F925
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Issue number4 40-4
StatePublished - 1996


  • Apical membrane
  • Proximal tubule
  • Sodium/hydrogen antiporter
  • Thick ascending limb

ASJC Scopus subject areas

  • Physiology


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