Inhibition of malaria parasite invasion into erythrocytes pretreated with membrane-active drugs.

Normal rhesus monkey erythrocytes were incubated with various membrane-active drugs (for 1 h at 37 degrees C) and after thorough washing, were exposed to infection with Plasmodium knowlesi in an invitro cultivation system. The ability of merozoites to infect with drug-pretreated erythrocytes was assessed both by counting the number of infected cells and by measuring the incorporation of [3H]isoleucine into parasite protein. Marked inhibition of invasion was observed with vinblastine and colchicine, at concentrations greater than 5 x 10(-4) M, respectively. At similar concentrations, cytochalasin B or amantadine had no apparent effect. The addition of 10(-3) M 3',5'-cAMP to the medium during the incubation in the presence of colchicine or vinblastine partially decreased the inhibitory effects. The effects of colchicine and vinblastine on parasite invasion may be correlated with a reversible alteration in erythrocyte conformation (spherocytosis) which occurs at similar drug concentrations to those above and which can be relieved by simultaneous incubation with cAMP. A possible mechanism of action is proposed.