In Vitro Research into the Action Mechanism of Antimalarial Drugs and Related Problems of Immunity

摘要

Penetration of mepacrine and quinine into both normal and parasitized erythrocytes increases with lowering of the pH, and does so to a greater extent with parasitized cells. The pH dependence does not replace the chloride shift. It is concluded that penetration of schizonticidal drugs into parasitized erythrocytes is governed by the accumulation of non-dialysable fatty acids which lowers the internal pH. Fatty acids are implicated in the destruction of erythrocytes by malaria parasites. The buffering capacity of AA, AS and SS haemoglobin was therefore examined and found to be considerably increased with sickle cell haemoglobin. This agrees well with the increase in positive charge due to the amino acid mutation in one Hb-chain and could provide a simple explanation of the selective advantage of sickle-cell trait in man, by preventing or retarding the release of merozoites and the associated intravascular haemolysis. (Author)