RENAL NA-S-I COTRANSPORTER NASI-1 IS INHIBITED BY HEAVY-METALS

Heavy metal intoxication leads to a number of reabsorptive and secreto ry defects in renal transport systems. We have studied the effects of several heavy metals on the expression of the renal Na-S-i cotransport er NaSi-1. NaSi-1 cRNA was injected into Xenopus oocytes, and Na-S-i c otransport activity was measured in the presence of mercury, lead, cad mium, or chromium. Mercury strongly inhibited NaSi-1 transport irrever sibly by reducing both maximal velocity (V-max) and Michaelis constant (K-m) for inorganic sulfate (S-i). Lead inhibited NaSi-1 transport re versibly by decreasing V-max but not K-m for S-i. Cadmium showed weak reversible inhibition of NaSi .. 1 transport by decreasing only NaSi-1 V-max. Chromium strongly inhibited NaSi-1 cotransport reversibly by r educing K-m for S-i by sevenfold, most probably by binding to the S-i site, due to the strong structural similarity between the CrO42- and S O42- substrates. In conclusion, this study presents an initial report demonstrating heavy metals inhibit renal brush border Na-S-i cotranspo rt via the NaSi-1 protein through various mechanisms and that this blo ckade may be responsible for sulfaturia following heavy metal intoxica tion.