PLATELET-ACTIVATING-FACTOR AND ITS METHOXY-ANALOG ET-18-OCH3 STIMULATE IMMEDIATE-EARLY GENE-EXPRESSION IN RAT ASTROGLIAL CULTURES

In the present paper we analyzed c-fos and zif/268 expression in rat p rimary astroglial cell cultures after treatment with Platelet-activati ng Factor (PAF) and its 2-O-methyl-analogue, 1-O-octadecyl-2-O-methoxy -glycero-3-phosphocholine (ET-18-OCH3). Both compounds, at a dose (2 m uM) that did not produce toxic effects on astroglial cells, induced a rapid and transient increase of c-fos and zif/268 mRNA level. Pretreat ment of astroglial cells with the PAF antagonist BN50730 (5 muM) 10 mi n prior to the addition of alkyl-phospholipids almost completely preve nted the activation of the immediate early genes. On the contrary tria zolam, another PAF inhibitor, did not block PAF induced gene expressio n when added to the medium at 5 muM concentration. ET-18-OCH3 effect o n gene expression is blocked by the same antagonist (BN50730) which is effective in inhibiting PAF effect on astrocytes, suggesting that bot h substances act through the same binding site. Results obtained suppo rt the view that astroglial cells are a cellular target for this lipid mediator, and, like macrophages, respond to its methoxy-analogue.