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Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland 4072, Australia
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 Xenopus oocytes, 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 (Vmax) and
Michaelis constant
(Km) for
inorganic sulfate (Si). Lead
inhibited NaSi-1 transport reversibly by decreasing
Vmax but not
Km for
Si. Cadmium showed weak reversible
inhibition of NaSi-1 transport by decreasing only NaSi-1
Vmax. Chromium
strongly inhibited NaSi-1 cotransport reversibly by reducing
Km for
Si by sevenfold, most probably by
binding to the Si site, due to the
strong structural similarity between the
C
and
substrates. In conclusion,
this study presents an initial report demonstrating heavy metals
inhibit renal brush border Na-Si
cotransport via the NaSi-1 protein through various mechanisms and that
this blockade may be responsible for sulfaturia following heavy metal
intoxication.
sodium-sulfate cotransport; brush-border membrane; Xenopus laevis oocytes; nephrotoxicity
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