Amplification of arachidonic acid metabolism in rat liver cells (the C-9 cell-line) by tosyl-L-phenylalanine chloromethyl ketone and phenylmethyl-sulfonyl fluoride.
In the presence of the protease inhibitors phenylmethyl-sulfonyl fluoride and N-tosyl-L-phenylalanine chloromethyl ketone, prostacyclin (PGI2) production by rat liver cells treated with epidermal growth factor, platelet-activating factor, 12-0-tetradecanoylphorbol-13-acetate (TPA), and TPA-type tumor promoters (teleocidin and aplysiatoxin) or 1-oleoyl-2-acetylglycerol is amplified. The PGI2 production stimulated by thapsigargin or exogenous arachidonic acid is not amplified. N-Tosyl-L-phenylalanine chloromethyl ketone also amplifies TPA's release of radioactivity from cells isotopically labeled with [3H]arachidonic acid. Indomethacin inhibits the amplification of PGI2 production but no the release of radioactivity. The presence of the protease inhibitors is not required for the amplification of PGI2 production. Prior incubation of the cells with these inhibitors, followed by their removal, still results in amplified PGI2 production by cells subsequently treated with TPA, 1-oleoyl-2-acetylglycerol, or platelet-activating factor but not that stimulated by exogenous arachidonic acid. While phenylmethyl-sulfonyl fluoride's amplification of PGI2 production by cells treated with TPA was blocked by prior incubation with TPA for 20 h, a similar block of amplification in EGF-treated cells was not observed.
Levine
L
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Department of Biochemistry, Brandeis University, Waltham, MA 02254, USA.
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D004075:Diglycerides / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008235:Lyngbya Toxins / Q000494:pharmacology; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology*
D002273:Carcinogens; D004075:Diglycerides; D008235:Lyngbya Toxins; D011480:Protease Inhibitors; D015842:Serine Proteinase Inhibitors; C022176:teleocidins; D016718:Arachidonic Acid; D014108:Tosylphenylalanyl Chloromethyl Ketone; C006610:aplysiatoxin; D010664:Phenylmethylsulfonyl Fluoride; C038237:1-oleoyl-2-acetylglycerol; D011464:Epoprostenol; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin