Intracellular pH does not affect drug extrusion by P-glycoprotein

Katalin Goda, László Balkay, Teréz Márián, Lajos Trón, Adorján Aszalós, Gábor Szabó

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Abstract

The intracellular pH (pH(i)) of cells exhibiting multidrug resistance (MDR) related to the expression of the P-glycoprotein (Pgp) is often more alkaline than that of the parental cells, as also observed for the KB-V1/KB-3-1 system in this paper. The possible role of an elevated pH(i) in Pgp-related MDR has been investigated by shifting back the pH(i) of the MDR+ cells to a more acidic value using the mobile proton ionophore carbonylcyanide m-chlorophenylhydrazone (CCCP). The influence of CCCP-evoked ΔpH(i) on relative daunorubicin (DNR) accumulation was similar in the case of several Pgp positive and negative cell lines, in view of flow cytometric and radioactive drug accumulation studies and measuring DNR levels in the medium in a flow-through system. Our data argue against a significant effect of pH(i) on Pgp pumping efficiency. However, an indirect connection between pH(i) regulation and the MDR phenotype is suggested by the fact that acidification of the external medium in the presence of verpamil could be observed exclusively in MDR+ cells.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalJournal of Photochemistry and Photobiology B: Biology
Volume34
Issue number2-3
DOIs
Publication statusPublished - Jul 1996

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Keywords

  • Intracellular pH
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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