The chemotherapy of rodent malaria, XXXI. The effect of some metabolic inhibitors upon chloroquine-induced pigment clumping (CIPC) in Plasmodium berghei.

The effect of metabolic inhibitors upon chloroquine-induced pigment clumping in intraerythrocytic Plasmodium berghei was studied in vitro. Oligomycin and venturicidin competitively inhibit the process with 'Ki' values of 0.18 and 0.41 mumol/l. DCCD, an agent thought to act upon a mitochondrial site close to that affected by oligomycin and venturicidin, causes pigment clumping in the absence of chloroquine ('Km' value 4.7 mumol/l). It is suggested that, after being concentrated in the cytoplasm by Fitch's high-affinity site, chloroquine interacts with a mitochondrial site, and this interaction initiates the pigment clumping process. Comparison of the effects of the ionophores 2,4,-dinitrophenol, monensin, and valinomycin indicates that a H gradient is involved at some stage in chloroquine-induced pigment clumping.