Metabolic acidosis regulates rat renal Na-S-i cotransport activity

Recently, we cloned a cDNA (NaS(i)-1) localized to rat renal proximal tubules and encoding the brushy-border membrane (BBC) Na gradient-dependent inorganic sulfate (S(i)) transpire protein (Na-S(i) cotransporter). The purpose of the present study was to determine the effect of metabolic acidosis (MA) on Na-S(i) cotransport activity and NaS(i)-1 protein and mRNA expression. In rats with MA for 24 h (but not 6 or 12 h), there was a significant increase in the fractional excretion of S(i), which was associated with a 2.4-fold decrease in BBM Na-S(i) cotransport activity. The decrease in Na-Si cotransport correlated with a 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2.2-fold decrease in cortical NaS(i)-1 mRNA abundance. The inhibitory effect of MA on BBM Na-S(i) cotransport was also sustained in rats with chronic (10 days) MA. In addition, in Xenopus laevis oocytes injected with mRNA from kidney cortex, there was a significant reduction in the induced Na-Si cotransport in rats with MA compared with control rats, suggesting that MA causes a decrease in the abundance of functional mRNA encoding the NaS(i)-1 cotransporter. These findings indicate that MA reduces S(i) reabsorption by causing decreases in BBM Na-S(i) cotransport activity and that decreases in the expression of NaS(i)-1 protein and mRNA abundance, at least in part, play an important role in the inhibition of Na-Si cotransport activity during MA