Abstract: | Recently, we cloned a cDNA(NaSi-1) localized to rat renalproximal tubules and encoding the brush-border membrane (BBM) Na gradient-dependent inorganic sulfate(Si) transport protein(Na-Si cotransporter). The purposeof the present study was to determine the effect of metabolic acidosis(MA) on Na-Si cotransport activity and NaSi-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 ofSi, which was associated with a2.4-fold decrease in BBM Na-Sicotransport activity. The decrease inNa-Si cotransport correlated witha 2.8-fold decrease in BBM NaSi-1 protein abundance and a 2.2-fold decrease in corticalNaSi-1 mRNA abundance. Theinhibitory effect of MA on BBMNa-Si 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-Si cotransport in ratswith MA compared with control rats, suggesting that MA causes adecrease in the abundance of functional mRNA encoding theNaSi-1 cotransporter. Thesefindings indicate that MA reduces Si reabsorption by causingdecreases in BBM Na-Si cotransport activity and that decreases in the expression ofNaSi-1 protein and mRNA abundance,at least in part, play an important role in the inhibition ofNa-Si cotransport activity during MA. |