Na-dependent transport of S-(1,2-dichlorovinyl)-L-cysteine by renal brush-border membrane vesicles

Stephen H. Wright, Theresa M. Wunz, J. North, James L. Stevens

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Cytotoxicity after exposure to the nephrotoxicant S-(1,2-dichloro- vinyl)-L-cysteine (DCVC) requires transport of this cysteine conjugate across the cell membrane. Although several basolateral transport pathways have been implicated in the uptake of this compound into renal proximal cells, the identity of the process or processes associated with transport across the luminal membrane is unclear. We used a preparation of luminal brush-border membrane vesicles to characterize the transport of [35S]DCVC in rabbit kidney. An inwardly directed Na-gradient stimulated the initial rate of DCVC uptake by 16-fold compared to uptake measured in the absence of Na+. The Na- dependent component of DCVC uptake was stimulated by imposition of an inside- negative electrical potential difference and was blocked by the presence of 5 mM unlabeled DCVC in the extravesicular solution. Transport of DCVC was adequately described by Michaelis-Menten kinetics with an apparent K(t) of 0.5 mM. DCVC uptake was blocked by the presence in the extravesicular solution of 10 mM concentrations of phenylalanine, leucine and cysteine, but not by glycine, proline, lysine, taurine, N-acetyl DCVC, p-aminohippurate, lactate or succinate. Unlabeled DCVC inhibited uptake of [14C]phenylalanine by a mechanism that exerted a greater effect on the apparent K(t) than on the J(max) of phenylalanine, implicating a possible competitive interaction between these compounds. The carrier-mediated permeability of DCVC (defined as the ratio of J(max)/K(t)) in luminal brush border membranes was as large as or larger than that reported for a battery of other organic electrolytes, including several amino acids and organic anions. We conclude that luminal transport of DCVC in rabbit proximal cells is limited to a single Na- cotransport process that also handles phenylalanine.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume285
Issue number1
StatePublished - Apr 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Fingerprint Dive into the research topics of 'Na-dependent transport of S-(1,2-dichlorovinyl)-L-cysteine by renal brush-border membrane vesicles'. Together they form a unique fingerprint.

  • Cite this