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 in piglet cultured glia derived from cerebral cortex and white matter. Levels of prostaglandins were determined using enzyme immunoassay. Baseline levels in media for prostaglandin F2 alpha (PGF2 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-keto-prostaglandin F1 alpha, prostaglandin E2, or leukotrienes C4/D4 were produced. PGF2 alpha levels in media did not increase in the presence of the vehicle for PDB (dimethyl sulfoxide) or 4 alpha-phorbol 12,13-didecanoate (PDD; a phorbol ester that does not activate protein kinase C) or when indomethacin (10 micrograms/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 cerebrovascular tone, and that PDB probably increases prostaglandin production via liberation of arachidonic acid by PKC-induced activation of phospholipase A2.
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Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1083.
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D015237:Dinoprost / Q000096:biosynthesis; D007546:Isoquinolines / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors; D013552:Swine
D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D047428:Protein Kinase Inhibitors; C008876:phorbol-12,13-didecanoate; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015237:Dinoprost