The in vitro effect of primaquine on red cell phospholipid metabolism

Primaquine converts erythrocytes into osmotically fragile spherocytes. Since primaquine increased the rate of acylation of erythrocyte lysophosphatidylcholine (LPC), it has been suggested that a deficiency of LPC is responsible for its hemolytic action. We have examined the validity of this hypothesis. In the absence of added lysophosphatides, primaquine slightly decreased the incorporation of albumin-bound palmitic acid-14C into phosphatidylcholine (PC) whereas that into phosphatidylethanolamine (PE) was more depressed. When unbound dispersions of fatty acid were used, red cells exposed to primaquine manifested a slight increase in palmitic acid-14C incorporation into PC whereas that into PE remained decreased. In the presence of exogenous LPC, control cells increased their incorporation of bound palmitic acid-14C into PC while decreasing it into PE. In these same experiments, red cells incubated with primaquine demonstrated a much greater enhancement of LPC acylation than control cells. Lysophosphatidylethanolamine acylation, while depressed, was still slightly greater than that of cells incubated with drug alone. The concentration of LPC in control and primaquine-treated erythrocytes incubated with exogenous LPC was comparable and was approximately five times that of cells not incubated with LPC. The osmotic fragility of erythrocytes correlated poorly with their concentration of LPC. The effect of primaquine on the incorporation of bound palmitic acid into erythrocyte PC was influenced by exogenous LPC with the reaction markedly increased in its presence but slightly depressed in its absence. The proposal that the hemolytic action of primaquine is due to a decrease in red cell LPC is not supported by the data.