Platelet-activating factor increases prostaglandin E(2) 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.
Teather
Lisa A
LA
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton Street, E25-604 Cambridge, MA 02139, USA. lteather@mit.edu
Lee
Robert K K
RK
Wurtman
Richard J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004224:Diterpenes; D004357:Drug Synergism; D005260:Female; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D009994:Osmolar Concentration; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D012997:Solvents / Q000494:pharmacology
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; D012997:Solvents; C053321:CV 6209; C053479:1-O-hexadecyl-2-N-methylcarbamylphosphatidylcholine; D016718:Arachidonic Acid; C045856:ginkgolide B; D015232:Dinoprostone