PHORBOL ESTER-INDUCED PROSTAGLANDIN PRODUCTION IN PIGLET CORTICAL ASTROGLIA

We examined effects of phorbol 12,13-dibutyrate (PDB), which activates protein kinase C (PKC), on prostaglandin and leukotriene production i n piglet cultured glia derived from cerebral cortex and white matter. Levels of prostaglandins were determined using enzyme immunoassay. Bas eline levels in media for prostaglandin F-2 alpha (PGF(2 alpha)) were 730 +/- 116 pg/ml and increased to 1,551 +/- 196 pg/ml at 10(-8) M PDB (P < 0.05) and to 2,182 +/- 190 pg/ml at 10(-6) M PDB (P < 0.05) (n = 16). Little or no 6-ketoprostaglandin F-1 alpha, prostaglandin E(2), or leukotrienes C-4/D-4 were produced. PGF(2 alpha), levels in media d id not increase in the presence of the vehicle for PDB (dimethyl sulfo xide) or 4(alpha)-phorbol 12,13-didecanoate (PDD; a phorbol ester that does not activate protein kinase C) or when indomethacin (10 mu g/ml) , quinacrine (10(-6) M), or isoquinolinylsulfonylmethyl piperazine (10 (-4) M) (an inhibitor of PKC activation) was coadministered with PDB. We conclude that glia can be important contributors of prostaglandins to extracellular-cerebrospinal fluids where they could influence cereb rovascular tone, and that PDB probably increases prostaglandin product ion via liberation of arachidonic acid by PKC-induced activation of ph ospholipase Az.