Effect of halogenated vinyl cysteine conjugates on renal tubular active transport

Christopher D. Hassall, A. Jay Gandolfi, Klaus Brendel

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Addition of halogenated vinyl cysteine conjugates to isolated rabbit kidney tubule suspensions resulted in a decrease in the active transport of para-aminohippuric acid (PAH) and tetraethylammonium bromide (TEA). At 10-5 M vinyl cysteine conjugate, tubule to medium accumulation ratios (T/M) were similar to those of controls while at 10-3 M the T/M values decreased to 1, indicating complete inhibition of active acummulation of PAH or TEA. The decreased active transport was not caused by inhibition of mitochondrial oxidation since incubations in the presence of 10-3 M halogenated vinyl cysteine did not inhibit tubule O2 utilization or production of 14CO2 from [14C]glucose or [14C]succinate. A mechanism is proposed whereby toxicity may result from covalent binding of an active intermediate, produced by enzyme cleavage, to membrane associated nucleophilic groups thereby decreasing active transport.

Original languageEnglish (US)
Pages (from-to)285-294
Number of pages10
JournalToxicology
Volume26
Issue number3-4
DOIs
StatePublished - Jan 1 1983

Keywords

  • 1,2-Dichlorovinyl cysteine
  • Active transport
  • Bioactivation
  • DCVC
  • Halogenated vinyl cysteine
  • Mitochondrial respiration
  • Nephrotoxin
  • Renal tubule

ASJC Scopus subject areas

  • Toxicology

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