Effects of okadaic acid on agonist-stimulated PGI2 production by rat liver cells (the C-9 cell line).
Preincubation of rat liver cells (the C-9 cell line) with okadaic acid (0.6 microM), a known inhibitor of protein-serine/threonine phosphate phosphatases 2A and 1, for 30 min amplified 6-keto-PGF1 alpha production stimulated by thapsigargin, thrombin, platelet activating factor (PAF), 12-O-tetradecanoylphorbol-13-acetate (TPA), the Ca2+ ionophore A-23187 and lysine-vasopressin (Lys.ADH) but not that stimulated by exogenous arachidonic acid. The amplification occurred within minutes after addition of the stimulators. The effect of preincubation was time dependent. Preincubation of the cells with okadaic acid (0.6 microM) for longer than 30 min decreased this amplification. The results suggest that inhibition of protein-serine/threonine phosphate phosphatase(s) can both positively and negatively regulate deesterification of phospholipids although the negative regulation may reflect a toxic response. Microcystin LR and nodularin, inhibitors of protein-serine/threonine phosphate phosphatases 2A and 1 in vitro, did not amplify 6-keto-PGF1 alpha production by PAF when incubated with intact cells.
Levine
L
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Department of Biochemistry, Brandeis University Waltham, MA 02254.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002460:Cell Line; D004988:Ethers, Cyclic / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011460:Prostaglandins F / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D004988:Ethers, Cyclic; D010972:Platelet Activating Factor; D011460:Prostaglandins F; D019319:Okadaic Acid; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D010749:Phosphoprotein Phosphatases; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; C100006:prostaglandin F1