title: Cyclooxygenase-2 mediates platelet-activating factor-induced prostaglandin E2 release from rat primary astrocytes.
abstract: The phospholipid mediator platelet-activating factor (PAF), and its non-hydrolyzable analog methylcarbamyl-PAF (mc-PAF) increase prostaglandin E(2) (PGE(2)) release from astrocyte-enriched cortical cell cultures. Cyclooxygenase (COX) enzymes--of which there are two known isoforms--convert arachidonic acid to prostaglandin (PG) H(2) (PGH(2)), which is further metabolized to various PGs, including PGE(2). COX-1 is generally considered to contribute to cell homeostasis, whereas COX-2 is thought to mediate inflammatory/immune PG formation. In this study we examined the involvement of the COX isoforms in PAF-induced PGE(2) release. Treatment of cells with the non-specific COX inhibitor indomethacin, or the specific COX-2 inhibitor NS-398, prior to mc-PAF stimulation completely blocked the PAF-induced release of PGE(2); treatment with more selective COX-1 inhibitors (i.e. piroxicam and SC-560) failed to significantly do so. These data suggest that COX-2 is responsible for PAF-mediated PGE(2) release in primary astrocytes.
authors.affiliation: Department of Brain and Cognitive Science, Massachusetts Institute of Technology 45 Carleton Street, E25-604, Cambridge, MA 02139, USA. lteather@mit.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Teather
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wurtman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology*; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010972:Platelet Activating Factor; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone