Uptake and efflux of chloroquine by chloroquine-resistant Plasmodium falciparum clones recently isolated in Africa.
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.
Bayoumi
R A
RA
Biochemistry Department, Faculty of Medicine and Health Sciences, UAE University, Al-Ain, United Arab Emirates.
Babiker
H A
HA
Arnot
D E
DE
D000349:Africa; D000818:Animals; D002738:Chloroquine / Q000378:metabolism* / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004351:Drug Resistance; D004912:Erythrocytes / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002738:Chloroquine; D014700:Verapamil; D003891:Desipramine