CHRONIC METABOLIC-ACIDOSIS INCREASES NHE3 PROTEIN ABUNDANCE IN RAT-KIDNEY

Chronic metabolic acidosis increases the activity of the proximal tubu le apical membrane Na/H antiporter, which is encoded predominantly by the NHE3 isoform. The present studies examined the effect of chronic m etabolic acidosis on apical membrane NHE3 protein abundance in rats. R ats subjected to NH4Cl in their drinking water developed a metabolic a cidosis, 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 o f the S1 and S2 segments of the proximal tubule and the thick ascendin g limb. NHE3 mRNA abundance was not significantly increased in these a nimals, whereas phosphoenolpyruvate carboxykinase and glyceraldehyde-3 -phosphate dehydrogenase mRNA abundances were significantly increased. These studies demonstrate that the increase in Na/H antiporter activi ty seen in metabolic acidosis involves an increase in NHE3 protein abu ndance, which is distributed along the proximal tubule and the thick a scending limb. In addition, these studies suggest that a component of this adaptation is unrelated to changes in NHE3 mRNA abundance.