Ral. Bayoumi et al., UPTAKE AND EFFLUX OF CHLOROQUINE BY CHLOROQUINE-RESISTANT PLASMODIUM-FALCIPARUM CLONES RECENTLY ISOLATED IN AFRICA, Acta Tropica, 58(2), 1994, pp. 141-149
In recently isolated African Plasmodium falciparum clones, the intrace
llular chloroquine concentration at steady-state, under standard cultu
re conditions, could not differentiate chloroquine-sensitive from resi
stant parasites. However, under an atmosphere of air the chloroquine-r
esistant P. falciparum clones released pre-accumulated [H-3]chloroquin
e more rapidly than sensitive clones. The very fast efflux of the prea
ccumulated drag from chloroquine-resistant (CQR) parasites resulted in
a differential in the drug retained by resistant and sensitive parasi
tes. The chloroquine-sensitive parasites retained 2-3 times more chlor
oquine than resistant parasites. The steady-state uptake of [H-3]chlor
oquine appeared to be enhanced by verapamil and desipramine in the chl
oroquine-resistant clones, while the opposite was observed with sensit
ive clones. This confirmed the suggestion that verapamil inhibits the
rapid efflux in CQR parasites resulting in a readily detectable increa
se in chloroquine accumulation. These observations indicate that the b
iochemical phenotypes of African chloroquine-resistant P. falciparum a
re similar to those reported from S.E. Asia and Latin America and are
consistent with a common molecular basis for the phenomenon.