The renal Na+-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxificafion

Birgitta C. Burckhardt, Britta Drinkuth, Christine Menzel, Angela König, Jürgen Steffgen, Stephen Wright, Gerhard Burckhardt

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The active transport of Krebs cycle intermediates, such as succinate, α-ketoglutarate, and citrate, is mediated by sodium-coupled transporters found in the luminal (NaDC-1) and basolateral plasma membranes (NaDC-3) of proximal tubule cells. This study used the two-electrode voltage clamp technique to examine steady-state currents associated with the influx of three sodium ions and one divalent dicarboxylate into oocytes expressing the sodium-dicarboxylate transporter from winter flounder kidney, fNaDC-3. The substrate concentration, where half-maximal current was observed (K0.5), was 30 μM for succinate. Besides 2,2-dimethylsuccinate, fNaDC-3 also accepted 2,3-dimethylsuccinate and the oral lead-chelating agent, meso-2,3-dimercaptosuccinate (DMSA or Succimer). Whereas the K0.5 for succinate and 2,2-dimethylsuccinate was independent of membrane voltage within -90 and -10 mV, K0.5 for 2,3-dimethylsuccinate and 2,3-dimercaptosuccinate increased with decreasing voltage, indicating a critical role of the position of the methyl- or sulfhydryl-group in voltage-sensitive affinity. In addition to meso-2,3-dimercaptosuccinate, fNaDC-3 translocated dimercaptopropane-1-sulfonate (DMPS or Dimaval), an oral chelator for the treatment of mercury intoxication. The chelates formed by HgCl2 and DMSA or DMPS and by Pb(NO3)2 and DMSA, however, were not translocated by fNaDC-3. The data suggest that NaDC-3 is an essential component in the delivery of uncomplexed antidotes for renal heavy metal detoxification.

Original languageEnglish (US)
Pages (from-to)2628-2638
Number of pages11
JournalJournal of the American Society of Nephrology
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

Fingerprint

Dicarboxylic Acid Transporters
Succimer
Unithiol
Heavy Metals
Succinic Acid
Kidney
Sodium
Chelating Agents
Flounder
Mercuric Chloride
Antidotes
Citric Acid Cycle
Active Biological Transport
Patch-Clamp Techniques
Mercury
Citric Acid
Oocytes
Electrodes
Cell Membrane
Ions

ASJC Scopus subject areas

  • Nephrology

Cite this

The renal Na+-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxificafion. / Burckhardt, Birgitta C.; Drinkuth, Britta; Menzel, Christine; König, Angela; Steffgen, Jürgen; Wright, Stephen; Burckhardt, Gerhard.

In: Journal of the American Society of Nephrology, Vol. 13, No. 11, 01.11.2002, p. 2628-2638.

Research output: Contribution to journalArticle

Burckhardt, Birgitta C. ; Drinkuth, Britta ; Menzel, Christine ; König, Angela ; Steffgen, Jürgen ; Wright, Stephen ; Burckhardt, Gerhard. / The renal Na+-dependent dicarboxylate transporter, NaDC-3, translocates dimethyl- and disulfhydryl-compounds and contributes to renal heavy metal detoxificafion. In: Journal of the American Society of Nephrology. 2002 ; Vol. 13, No. 11. pp. 2628-2638.
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AU - Drinkuth, Britta

AU - Menzel, Christine

AU - König, Angela

AU - Steffgen, Jürgen

AU - Wright, Stephen

AU - Burckhardt, Gerhard

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