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Molecular Pharmacology

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Research ArticleArticle

Mechanisms of Action of 2,3-Dimercaptopropane-1-sulfonate and the Transport, Disposition, and Toxicity of Inorganic Mercury in Isolated Perfused Segments of Rabbit Proximal Tubules

Rudolfs K. Zalups, Lisa D. Parks, Vernon T. Cannon and Delon W. Barfuss
Molecular Pharmacology August 1998, 54 (2) 353-363; DOI: https://doi.org/10.1124/mol.54.2.353
Rudolfs K. Zalups
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Lisa D. Parks
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Vernon T. Cannon
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Delon W. Barfuss
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Abstract

Mechanisms by which the dithiol chelating agent 2,3-dimercaptopropane-1-sulfonate (DMPS) significantly alters the renal tubular transport, accumulation, and toxicity of inorganic mercury were studied in isolated perfused pars recta (S2) segments of proximal tubules of rabbits. Addition of 200 μm DMPS to the bath provided complete protection from the toxic effects of 20 μm inorganic mercury in the lumen. The protection was linked to decreased uptake and accumulation of mercury. Additional data indicated that, when DMPS and inorganic mercury were coperfused through the lumen, very little inorganic mercury was taken up from the lumen. We also obtained data indicating that DMPS is transported by the organic anion transport system and that this transport is linked to the therapeutic effects of DMPS. Interestingly, very little inorganic mercury was taken up and no cellular pathological changes were detected when inorganic mercury and DMPS were added to the bath. We also tested the hypothesis that DMPS can extract cellular mercury while being transported from the bath into the luminal compartment. Our findings showed that, when DMPS was applied to the basolateral membranes of S2 segments after they had been exposed to mercuric conjugates of glutathione of the laminal membrane, the tubular content of mercury was greatly reduced and the rates of disappearance of mercury from the lumen changed from positive values to markedly negative values. We conclude that inorganic mercury is extracted from proximal tubular cells by a transport process involving the movement of DMPS from the bathing compartment to the luminal compartment.

Footnotes

    • Received March 13, 1998.
    • Accepted April 17, 1998.
  • Send reprint requests to: Dr. Rudolfs K. Zalups, Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College Street, Macon, GA 31207. E-mail: zalups.rk{at}gain.mercer.edu

  • Support for this study came from National Institute of Environmental Health Sciences Grants ES05157 (R.K.Z.) and ES05980 (R.K.Z. and D.W.B.).

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 54 (2)
Molecular Pharmacology
Vol. 54, Issue 2
1 Aug 1998
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Research ArticleArticle

Mechanisms of Action of 2,3-Dimercaptopropane-1-sulfonate and the Transport, Disposition, and Toxicity of Inorganic Mercury in Isolated Perfused Segments of Rabbit Proximal Tubules

Rudolfs K. Zalups, Lisa D. Parks, Vernon T. Cannon and Delon W. Barfuss
Molecular Pharmacology August 1, 1998, 54 (2) 353-363; DOI: https://doi.org/10.1124/mol.54.2.353

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Research ArticleArticle

Mechanisms of Action of 2,3-Dimercaptopropane-1-sulfonate and the Transport, Disposition, and Toxicity of Inorganic Mercury in Isolated Perfused Segments of Rabbit Proximal Tubules

Rudolfs K. Zalups, Lisa D. Parks, Vernon T. Cannon and Delon W. Barfuss
Molecular Pharmacology August 1, 1998, 54 (2) 353-363; DOI: https://doi.org/10.1124/mol.54.2.353
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