Platelet-activating factor increases prostaglandin E 2 release from astrocyte-enriched cortical cell cultures

Abstract

The phospholipid mediator platelet-activating factor (PAF) increased the release of prostaglandin E 2 (PGE 2) from astrocyte-enriched cortical cell cultures in a concentration- and time-dependent manner. The nonhydrolyzable PAF analog methylcarbamyl-PAF (mc-PAF), the PAF intermediate lyso-PAF, and arachidonic acid (AA) also produced this effect. In contrast, phosphatidlycholine (PC) and lyso-PC, lipids that are structurally similar to PAF and lyso-PAF, had no effect on PGE 2 production, suggesting that PAF-induced PGE 2 release is not the consequence of nonspecific phospholipid-induced membrane perturbation. Antagonism of intracellular PAF binding sites completely abolished the ability of mc-PAF and lyso-PAF to mobilize PGE 2, and attenuated the AA effect. Antagonism of the G-protein-coupled PAF receptor in plasma membranes had no significant effect on mc-PAF, lyso-PAF or AA-induced PGE 2 release. Based on the present findings, we hypothesize that intracellular PAF is a physiologic stimulus of PGE 2 production in astrocytes.