Accumulation of chloroquine by membrane preparations from Plasmodium falciparum

Barbara L. Herwaldt, Paul H. Schlesinger, Donald J. Krogstad

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Chloroquine susceptibility and resistance have been associated respectively with the uptake and efflux of chloroquine by Plasmodium falciparum. We made membrane preparations from parasitized and unparasitized red cells in order to study chloroquine accumulation in a cell-free system. The accumulation of [3H]chloroquine by these preparations is inhibited by unlabeled chloroquine and thus is specific. Only membranes from parasitized red cells demonstrate time-dependent chloroquine accumulation; membranes from unparasitized red cells do not. Chloroquine accumulation is eliminated by detergent (0.05% Triton X-100) and reduced by a hypertonic medium, consistent with accumulation inside membrane vesicles rather than binding to membranes. Accumulation is energy dependent; it has a specific requirement for ATP, which cannot be replaced with GTP, CTP, UTP, TTP or ADP, an apparent Km of 21 μM and an apparent Vmax of 4.6 pmol (mg protein)-1 h-1. Vesicle acidification is MgATP dependent, and is reversed by NH4Cl. Chloroquine accumulation is inhibited by reduced medium pH, N-ethylmaleimide or oligomycin, but not by vanadate or ouabain. These studies demonstrate that membrane vesicles prepared from parasitized red cells provide a model system for the study of chloroquine accumulation by P. falciparum.

Original languageEnglish
Pages (from-to)257-267
Number of pages11
JournalMolecular and Biochemical Parasitology
Volume42
Issue number2
DOIs
StatePublished - Jan 1 1990

Keywords

  • Acidification
  • Chloroquine
  • Chloroquine accumulation
  • Malaria
  • Membrane vesicle
  • Plasmodium falciparum

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