Ferriprotoporphyrin IX: role in chloroquine susceptibility and resistance in malaria.
A review of all available evidence supports the hypothesis that FP is the receptor for chloroquine and mediator of its antimalarial activity. In accord with this hypothesis, previously unpublished experiments are described which demonstrate no effect of verapamil on chloroquine accumulation when chloroquine-resistant malaria parasites are nearly totally deficient in FP. Not all chloroquine-resistant parasites are so deficient in FP, however. It is important, therefore, to understand how the concentration of the toxic form of FP, which binds chloroquine, is regulated in erythrocytes infected with pigmented malaria parasites. This regulatory process involves the conversion of toxic FP to nontoxic aggregates (oligomers) of FP which have low oxygen contents. It is also possible that toxic FP is detoxified by decomposition, for example, by hydrogen peroxide.
Fitch
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Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63104.
D000818:Animals; D002738:Chloroquine / Q000378:metabolism* / Q000494:pharmacology; D004351:Drug Resistance; D004912:Erythrocytes / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives*; D006427:Hemin / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D008288:Malaria / Q000097:blood* / Q000469:parasitology; D010961:Plasmodium / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D006454:Hemoglobins; D006418:Heme; D006427:Hemin; D002738:Chloroquine; D014700:Verapamil