Reversal of multidrug resistance by valinomycin is overcome by CCCP

Katalin Goda, Zoltán Krasznai, Rezso Gáspár, Jan Lankelma, Hans V. Westerhoff, Sándor Damjanovich, Gábor Szabó

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Reversal of P-glycoprotein-mediated multidrug resistance by valinomycin is overcome by die proton ionophore, CCCP. This effect, a complete suppression of the 5- to 10-fold valinomycin-induced reversal ('re-reversal'), exhibits a sharp extracellular potassium concentration ([K+(o)]) dependence. It is observed at [K+(o)] > 2-4 mM and not at [K+(o)] ≤ 2 mM, in the case of the fluorescent substrates rhodamine 123 and daunorubicin. The fact that 're-reversal' is detected only for the combination of CCCP with valinomycin raises the possibility that a direct interaction between these ionophores may explain the phenomenon. We show spectroscopic evidence of such an interaction, with a [K+(o)]-dependence similar to that of the 're-reversal.' These data suggest that the reversal of P-glycoprotein activity by valinomycin can be compromised by anionic compounds such as CCCP due to complex formation. More generally, molecular interactions involving P-glycoprotein substrates or reversing agents may significantly affect drug accumulation in multidrug resistant cells.

Original languageEnglish
Pages (from-to)306-310
Number of pages5
JournalBiochemical and biophysical research communications
Volume219
Issue number2
DOIs
Publication statusPublished - Feb 15 1996

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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