CHLOROQUINE RESISTANCE IN MALARIA: A DEFICIENCY OF CHLOROQUINE BINDING*

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RESUMO

Chloroquine-14C was used to study the processes which concentrate chloroquine in mouse red blood cells infected with chloroquine-sensitive or with chloroquine-resistant Plasmodium berghei. The initial rates of uptake and exchange of chloroquine-14C were both too fast to measure, yet large concentration gradients were maintained by the cells. When red blood cells were exposed to 10-8M chloroquine at 22°C, with pH between 7.2 and 7.4, steady-state gradients of chloroquine-14C were approximately 600:1 (cells:medium) for cells infected with chloroquine-sensitive parasites, 100:1 for cells comparably infected with chloroquine-resistant parasites, and 14:1 for uninfected cells. The processes responsible for these gradients were saturable, in agreement with the proposal of chloroquine binding to cellular constituents. No degradation of chloroquine was detected.

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