Platelet-activating factor increases prostaglandin E2 release from astrocyte-enriched cortical cell cultures

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. (C) 2002 Elsevier Science B.V. All rights reserved.