Chronic metabolic acidosis increases NaDC-1 mRNA and protein abundance in rat kidney

Background: Chronic metabolic acidosis increases, while alkali feeding inhibits, proximal tubule citrate absorption. The activity of the apical membrane Na⁺/citrate cotransporter is increased in metabolic acidosis, but is not altered by alkali feeding. Methods: Renal cortical mRNA and brush border membrane protein abundances of sodium/dicarboxylate-1 (NaDC-1), the apical membrane Na⁺/citrate transporter, were measured. Results: By immunohistochemistry, NaDC-1 was localized to the apical membrane of the proximal tubule. Chronic metabolic acidosis caused an increase in NaDC-1 protein abundance that was maximal in the S2 segment and that increased with time. Metabolic acidosis also increased NaDC-1 mRNA abundance, but this was first seen at three hours and correlated with the severity of the metabolic acidosis. Alkali feeding had no effect on NaDC-1 protein or mRNA abundance. Conclusions: Chronic metabolic acidosis increases renal cortical NaDC-1 mRNA abundance and apical membrane NaDC-1 protein abundance, while alkali feeding is without effect on NaDC-1.