Binding of mercury in renal brush-border and basolateral membrane-vesicles.
The influence of the thiols L-cysteine (CYS), glutathione (GSH), and 2,3-dimercapto-1-propanesulfonate (DMPS) on the binding and transport of inorganic mercury (Hg2+) in luminal (brush-border) and basolateral membrane-vesicles isolated from the kidneys of rats was studied using radiolabeled mercury (203HgCl2). Membrane-vesicles were exposed to 1, 10, or 100 microM Hg2+ in the presence or absence of a 3:1 or 10:1 mole-ratio of CYS, GSH, or DMPS relative to Hg2+. Equilibration of mercury with the membrane-vesicles occurred very rapidly, essentially being complete within 5 sec. By 60 sec, binding accounted for 87-97% of intravesicular Hg2+ in the absence of exogenous thiols. All three thiols significantly reduced the fraction of binding, with DMPS being the most effective agent. CYS enhanced the association of Hg2+ with luminal membrane-vesicles relative to that when Hg2+ was added alone, suggesting that conjugation of Hg2+ with CYS promotes the transport of low concentrations of Hg2+. In contrast, an excess of either GSH or DMPS relative to Hg2+ interfered significantly with both the binding and transport of Hg2+ into either luminal or basolateral membrane-vesicles. In summary, the present study is the first to describe the association of Hg2+ with renal luminal and basolateral membrane-vesicles. Evidence was obtained for the involvement of a Hg2+-CYS conjugate as a mechanism by which Hg2+ uptake and binding to luminal membranes occur and for an inhibitory effect of GSH and the chelator DMPS with regard to Hg2+ uptake and binding, demonstrating that extracellular thiols can modulate significantly the renal accumulation of Hg2+.
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Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, GA 31207, USA.
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008628:Mercury / Q000378:metabolism* / Q000494:pharmacology; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014494:Unithiol / Q000494:pharmacology
D014494:Unithiol; D008628:Mercury; D005978:Glutathione; D003545:Cysteine