Uptake and efflux of chloroquine by chloroquine-resistant Plasmodium falciparum clones recently isolated in Africa
Identifieur interne : 002C58 ( Main/Exploration ); précédent : 002C57; suivant : 002C59Uptake 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 :
- Acta Tropica [ 0001-706X ] ; 1994.
English descriptors
- KwdEn :
- Teeft :
- Acta tropica, Babiker, Bayoumi, Biochemical phenotypes, Chloroquine, Chloroquine accumulation, Chloroquine resistance, Chloroquine uptake, Clone, Culture conditions, Culture flasks, Desipramine, Drug accumulation, Drug resistance, East asia, Eastern sudan, Efflux, Efflux experiment, Erythrocyte, External medium, Falciparum, Falciparum clones, Food vacuole, Geary, Ginsburg, Hour incubation, Krogstad, Parasite, Parasitized, Plasmodium, Plasmodium falciparum, Previous reports, Rapid efflux, Sensitive clones, Sensitive parasites, Separate experiments, Sigma chemical company, Standard culture conditions, Sudan, Time point, Verapamil.
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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<front><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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