Renal Na-Si cotransporter NaSi-1 is inhibited by heavy metals.

Heavy metal intoxication leads to a number of reabsorptive and secretory defects in renal transport systems. We have studied the effects of several heavy metals on the expression of the renal Na-Si cotransporter NaSi-1. NaSi-1 cRNA was injected into Xenopusoocytes, and Na-Si cotransport activity was measured in the presence of mercury, lead, cadmium, or chromium. Mercury strongly inhibited NaSi-1 transport irreversibly by reducing both maximal velocity ( V max) and Michaelis constant ( K m) for inorganic sulfate (Si). Lead inhibited NaSi-1 transport reversibly by decreasing V max but not K m for Si. Cadmium showed weak reversible inhibition of NaSi-1 transport by decreasing only NaSi-1 V max. Chromium strongly inhibited NaSi-1 cotransport reversibly by reducing K m for Si by sevenfold, most probably by binding to the Si site, due to the strong structural similarity between the C[Formula: see text] and[Formula: see text] substrates. In conclusion, this study presents an initial report demonstrating heavy metals inhibit renal brush border Na-Sicotransport via the NaSi-1 protein through various mechanisms and that this blockade may be responsible for sulfaturia following heavy metal intoxication.