Efflux of chloroquine from Plasmodium falciparum: Mechanism of chloroquine resistance

Donald J. Krogstad, Ilya Y. Gluzman, Dennis E. Kyle, Ayoade M.J. Oduola, Samuel K. Martin, Wilbur K. Milhous, Paul H. Schlesinger

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Chloroquine-resistant Plasmodium falciparum accumulate significantly less chloroquine than susceptible parasites, and this is thought to be the basis of their resistance. However, the reason for the lower accumulation of chloroquine was unknown. The resistant parasite has now been found to release chloroquine 40 to 50 times more rapidly than the susceptible parasite, although their initial rates of chloroquine accumulation are the same. Verapamil and two other calcium channel blockers, as well as vinblastine and daunomycin, each slowed the release and increased the accumulation of chloroquine by resistant (but not susceptible) Plasmodium falciparum. These results suggest that a higher rate of chloroquine release explains the lower chloroquine accumulation, and thus the resistance observed in resistant Plamodium falciparum.

Original languageEnglish
Pages (from-to)1283-1285
Number of pages3
Issue number4831
StatePublished - Jan 1 1987

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