TY - JOUR T1 - Heme Polymerase Activity and the Stage Specificity of Antimalarial Action of Chloroquine JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 108 LP - 112 VL - 282 IS - 1 AU - Augustine U. Orjih Y1 - 1997/07/01 UR - http://jpet.aspetjournals.org/content/282/1/108.abstract N2 - Plasmodium falciparum lysate, prepared from 2.7 × 107 ring-infected erythrocytes and incubated with hemoglobin in sodium acetate at pH 5, incorporated a mean of 1.6 nmol of ferriprotoporphyrin IX (FP) into hemozoin in 18 to 22 hr. A similar preparation of trophozoite lysate incorporated a mean of 3.6 nmol of FP into hemozoin in 4 to 6 hr. These findings indicate differences between heme polymerase activity (hemozoin production) at the ring and trophozoite stages of malaria parasites. Intracellular hemozoin production was 90% inhibited at the ring and trophozoite stages by 0.5 and 7 nmol of chloroquine/106 infected erythrocytes. respectively. The inhibition killed the rings but not the trophozoites, suggesting that mature parasites may have a mechanism for protecting themselves against chloroquine-FP toxicity. The American Society for Pharmacology and Experimental Therapeutics ER -