Platelet-activating factor phosphatidate, but not platelet-activating factor, is a powerful calcium ionophore in the human red cell

Abstract

Platelet-activating factor (1-0-alkyl-2-acetyl- sn-glyceryl-3-phosphorylcholine, PAF) is a potent inducer of shape-change, aggregation and secretion in platelets. PAF causes a rapid increase in intracellular calcium, but has no calcium gating effect in intact lipid bilayers. Human red cells (RBC) did not metabolize either PAF or PAF-phosphatidate (PAF-PA). While PAF (10 μM) was devoid of calcium ionophoretic activity, PAF-PA (1–5 μM) stimulated calcium influx into intact human RBC. In addition, PAF-PA (1–10 μM), but not PAF (10 μM), elicited a series of satellite effects related to the rise of intracellular calcium: 1) increased efflux of intracellular potassium (Gàrdos effect); 2) alkalinization of unbuffered RBC suspensions; 3) stimulation of ATP consumption and production, and enhancement of glycolytic flux with crossover at the glyceraldehyde 3-phosphate dehydrogenase step. These effects exactly duplicate those brought about by the calcium ionophore A23187. The ionophoretic potency of PAF-PA was about half that of A23187. Approximately the same concentrations of PAF-PA as those that stimulate calcium influx into RBC elicit full aggregatory response in human platelets. It is possible that transformation of PAF into PAF-PA by the combined action of phospholipase C and diacylglycerol kinase contributes to the increase of calcium influx in platelets.