Entry and Distribution of Chlorpromazine and Vinblastine into Human Erythrocytes during Endocytosis 1

Abstract

Abstract

Drug-induced endocytosis in intact human erythrocytes is a membrane-mediated event involving membrane invagination and fusion. The drugs capable of inducing endocytosis are amphipathic cations and it was thought that they intercalate themselves into the relatively electronegative cytosolic portion of the phospholipid bilayer. The current studies show that at concentrations that produce endocytosis vinblastine and chlorpromazine are not only concentrated in the red cell membrane compartment but reach high levels in the cytosol as well. The suspending medium can produce impressive effects on the extent of endocytosis. Sodium lactate enhances chlorpromazine and vinblastine endocytosis without altering the incorporation or distribution of these agents. Sucrose enhances chlorpromazine and inhibits vinblastine endocytosis, and while it produces no effects on chlorpromazine incorporation it inhibits vinblastine incorporation, thus in part accounting for its effects. It is proposed that the amphipathic drugs that cause endocytosis produce both membrane and cytosolic alterations which interact to result in the membrane internalization.