AJP - Renal Physiology, Vol 271, Issue 4 926-F930, Copyright © 1996 by American Physiological Society

ARTICLES

Heavy metals inhibit Pi-induced currents through human brush-border NaPi-3 cotransporter in Xenopus oocytes

C. A. Wagner, S. Waldegger, H. Osswald, J. Biber, H. Murer, A. E. Busch and F. Lang
Institute of Physiology 1, Eberhard-Karls-Universitat Tubingen, Germany.

Heavy metal intoxication with Hg2+, Pb2+ and Cd2+ commonly leads to phosphaturia. In this study, we examined the effects of these heavy metals on 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'-dithiobis(2-nitrobenzoic acid). Hg(2+)- and DTNP-mediated inhibition of Ip was reversible only in the presence of the reducing agent 2,3-dihydroxybutane-1,4-dithiol. Cd2+ and Pb2+ also inhibited Ip. However, while CD2+ did not significantly alter the apparent affinity for Pi, the apparent concentration needed for half-maximal current (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(+)-adenosinetriphosphatase 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 Ip 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.

This article has been cited by other articles:

				A. Mercado, P. de los Heros, N. Vazquez, P. Meade, D. B. Mount, and G. Gamba Functional and molecular characterization of the K-Cl cotransporter of Xenopus laevis oocytes Am J Physiol Cell Physiol, August 1, 2001; 281(2): C670 - C680. [Abstract] [Full Text] [PDF]

				H. Murer, N. Hernando, I. Forster, and J. Biber Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms Physiol Rev, October 1, 2000; 80(4): 1373 - 1409. [Abstract] [Full Text] [PDF]

				F. THÉVENOD and J. M. FRIEDMANN Cadmium-mediated oxidative stress in kidney proximal tubule cells induces degradation of Na+/K+-ATPase through proteasomal and endo-/lysosomal proteolytic pathways FASEB J, October 1, 1999; 13(13): 1751 - 1761. [Abstract] [Full Text]

				D. Markovich and D. Knight Renal Na-Si cotransporter NaSi-1 is inhibited by heavy metals Am J Physiol Renal Physiol, February 1, 1998; 274(2): F283 - F289. [Abstract] [Full Text] [PDF]

				N. Vazquez, A. Monroy, E. Dorantes, R. A. Munoz-Clares, and G. Gamba Functional differences between flounder and rat thiazide-sensitive Na-Cl cotransporter Am J Physiol Renal Physiol, April 1, 2002; 282(4): F599 - F607. [Abstract] [Full Text] [PDF]