Serveur d'exploration Chloroquine

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Uptake and efflux of chloroquine by chloroquine-resistant Plasmodium falciparum clones recently isolated in Africa

Identifieur interne : 002C58 ( Main/Exploration ); précédent : 002C57; suivant : 002C59

Uptake and efflux of chloroquine by chloroquine-resistant Plasmodium falciparum clones recently isolated in Africa

Auteurs : Riad A. L. Bayoumi [Émirats arabes unis] ; Hamza A. Babiker [Royaume-Uni] ; David E. Arnot [Royaume-Uni]

Source :

RBID : ISTEX:4E4943875C58033BF66BED899391BFE9E8B68631

English descriptors

Abstract

Abstract: In recently isolated African Plasmodium falciparum clones, the intracellular chloroquine concentration at steady-state, under standard culture conditions, could not differentiate chloroquine-sensitive from resistant parasites. However, under an atmosphere of air the chloroquine-resistant P. falciparum clones released pre-accumulated [3H]chloroquine more rapidly than sensitive clones. The very fast efflux of the pre-accumulated drug from chloroquine-resistant (CQR) parasites resulted in a differential in the drug retained by resistant and sensitive parasites. The chloroquine-sensitive parasites retained 2–3 times more chloroquine than resistant parasites. The steady-state uptake of [3H]chloroquine appeared to be enhanced by verapamil and desipramine in the chloroquine-resistant clones, while the opposite was observed with sensitive clones. This confirmed the suggestion that verapamil inhibits the rapid efflux in CQR parasites resulting in a readily detectable increase in chloroquine accumulation. These observations indicate that the biochemical phenotypes of African chloroquine-resistant P. falciparum are similar to those reported from S.E. Asia and Latin America and are consistent with a common molecular basis for the phenomenon.

Url:
DOI: 10.1016/0001-706X(94)90053-1


Affiliations:


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Le document en format XML

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<div type="abstract" xml:lang="en">Abstract: In recently isolated African Plasmodium falciparum clones, the intracellular chloroquine concentration at steady-state, under standard culture conditions, could not differentiate chloroquine-sensitive from resistant parasites. However, under an atmosphere of air the chloroquine-resistant P. falciparum clones released pre-accumulated [3H]chloroquine more rapidly than sensitive clones. The very fast efflux of the pre-accumulated drug from chloroquine-resistant (CQR) parasites resulted in a differential in the drug retained by resistant and sensitive parasites. The chloroquine-sensitive parasites retained 2–3 times more chloroquine than resistant parasites. The steady-state uptake of [3H]chloroquine appeared to be enhanced by verapamil and desipramine in the chloroquine-resistant clones, while the opposite was observed with sensitive clones. This confirmed the suggestion that verapamil inhibits the rapid efflux in CQR parasites resulting in a readily detectable increase in chloroquine accumulation. These observations indicate that the biochemical phenotypes of African chloroquine-resistant P. falciparum are similar to those reported from S.E. Asia and Latin America and are consistent with a common molecular basis for the phenomenon.</div>
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