Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX and is independent of NHE activity in Plasmodium falciparum.

摘要: Here we provide definitive evidence that chloroquine (CQ) uptake in Plasmodium falciparum is determined by binding to ferriprotoporphyrin IX (FPIX). Specific proteinase inhibitors block the degradation of hemoglobin and stop generation FPIX also inhibit CQ uptake. Food vacuole enzymes can generate cell-free binding, using human as a substrate. This accounts for into intact cells subject identical inhibitor specificity. Inhibition amiloride derivatives occurs because inhibition CQ-FPIX rather than Na+/H+ exchanger (NHE). parasite NHE sodium-free medium does not nor it alter ability amilorides resistance characterized reduced affinity reversible verapamil. Diverse compounds are known disrupt lysosomal pH mimic verapamil effect. These effects seen due stimulation NHE. We propose these increase accumulation overcome increasing lysosomes endosomes, thereby causing an increased FPIX.