Metabolic acidosis regulates rat renal Na-Si cotransport activity

Recently, we cloned a cDNA(NaS_i-1) localized to rat renalproximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate(S_i) transport protein(Na-S_i cotransporter). The purposeof the present study was to determine the effect of metabolic acidosis(MA) on Na-S_i cotransport activity and NaS_i-1 protein and mRNAexpression. In rats with MA for 24 h (but not 6 or 12 h), there was asignificant increase in the fractional excretion ofS_i, which was associated with a2.4-fold decrease in BBM Na-S_icotransport activity. The decrease inNa-S_i cotransport correlated witha 2.8-fold decrease in BBM NaS_i-1 protein abundance and a 2.2-fold decrease in corticalNaS_i-1 mRNA abundance. Theinhibitory effect of MA on BBMNa-S_i cotransport was alsosustained in rats with chronic (10 days) MA. In addition, inXenopus laevis oocytes injected withmRNA from kidney cortex, there was a significant reduction in theinduced Na-S_i cotransport in ratswith MA compared with control rats, suggesting that MA causes adecrease in the abundance of functional mRNA encoding theNaS_i-1 cotransporter. Thesefindings indicate that MA reduces S_i reabsorption by causingdecreases in BBM Na-S_i cotransport activity and that decreases in the expression ofNaS_i-1 protein and mRNA abundance,at least in part, play an important role in the inhibition ofNa-S_i cotransport activity during MA.