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

Recently, me cloned a cDNA (NaSi-1) localized to rat renal proximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorgan ic sulfate (S-i) transport protein (Na-S-i cotransporter). The purpose of t he present study was to determine the effect of metabolic acidosis (MA) on Na-S-i cotransport activity and NaSi-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 decre ase in BBM Na-S-i cotransport activity. The decrease in Na-S-i cotransport correlated with a 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2 .2-fold decrease in cortical NaSi-1 mRNA abundance. The inhibitory effect o f MA on BBM Na-Si cotransport was also sustained in rats with chronic (10 d ays) MA. In addition, in Xenopus laevis oocytes injected with mRNA from kid ney cortex, there was a significant reduction in the induced Na-S-i cotrans port in rats with MA compared with control rats, suggesting that MA causes a decrease in the abundance of functional mRNA encoding the NaSi-1 cotransp orter. These findings indicate that MA reduces Si reabsorption by causing d ecreases in BBM Na-S-i cotransport activity and that decreases in the expre ssion of NaSi-1 protein and mRNA abundance, at least in part, play an impor tant role in the inhibition of Na-S-i cotransport activity during MA.