Heavy metals inhibit pi - induced currents through human brush
border na+/phosphate - cotransporter (napi-3) expressed in xenopus
oocytes.
Wagner, Carsten A., Siegfried Waldegger, Hartmut O[beta]wald,
J[umlaut]urg Biber, Heini Murer, Andreas E. Busch, and Florian Lang.
Institute of Physiology I 3 Institute of Physiology, Eberhard
-Karls-Universit[umlaut]at T[umlaut]ubingen University of
Z[umlaut]urich, Gmelinstr. 5 Winterthurerstr. 190, D-72076
T[umlaut]ubingen, Germany CH-8057 Z[umlaut]urich, Switzerland,
Institute of Pharmacology, Eberhard-Karls-Universit[umlaut]at,
Wilhelmstr. 56, D-72072 T[umlaut]ubingen, Germany
APStracts 3:0128F, 1996.
Heavy metal intoxication with Hg2+, Pb2+ and Cd2+ commonly lead to
phosphaturia. In this study, we examined the effects of these heavy
metals on inorganic phosphate (Pi)-induced currents (Ip) through
NaPi-3, the human renal cotransporter for Na+ and Pi. Hg2+ inhibited
IP in a dose- and time-dependent fashion. Hg2+ decreased the
extrapolated maximal current but did not alter the apparent affinity
for Pi. This inhibition was also observed with the membrane permeable
oxidizing agent 2,2'-Dithio-bis(5-Nitropyridine) (DTNP), but not with
the membrane impermeable 5,5'-Dithio-bis (2-Nitrobenzoic acid (DTNB).
Hg2+- and DTNP-mediated inhibition of IP was reversible only in the
presence of the reducing agent 2,3-Dihydroxybutane-1,4-dithiol (DTE).
Cd2+ and Pb2+ also inhibited IP. However, while Cd2+ did not
significantly alter the apparent affinity for Pi, the Km for Pi was
increased by Pb2+. In contrast to Hg2+, the inhibition of IP by Cd2+
and Pb2+ was rapidly reversible upon washout. In the presence of the
Na+/K+-ATPase inhibitor ouabain Ip was not reduced and the effects of
the heavy metals were maintained. In summary, the three heavy metals
Hg2+, Cd2+ and Pb2+ inhibit Pi -induced currents through the Na+/Pi
-cotransporter NaPi-3 by distinct mechanisms. Heavy metal mediated
inhibition of NaPi-3 may be responsible for the phosphaturia observed
after intoxication with these compounds.
Received 8 November 1995; accepted in final form 19 June 1996.
APS Manuscript Number F380-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996