Effects of the protein kinase inhibitors, staurosporine and K-252a, on PGI2 production by rat liver cells (the C-9 cell line).
Staurosporine and K-252a, known inhibitors of several protein kinases, stimulated PGI2 production (measured as 6-keto-PGF1 alpha) in rat liver cells (the C-9 cell line). Preincubation of the rat liver cells with staurosporine or K-252a enhanced the PGI2 production stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), platelet activating factor (PAF) and the Ca2(+)-ionophore A-23187, but not the PGI2 synthesis stimulated by exogenous arachidonic acid. These results suggest that phosphorylation of some proteins or certain amino acids on a protein can regulate arachidonic acid metabolism probably in the pathway leading to deesterification of phospholipids.
Levine
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Department of Biochemistry, Brandeis University, Waltham, MA 02254.
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis*; D026121:Indole Alkaloids; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011863:Radioimmunoassay; D051381:Rats; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D002227:Carbazoles; D026121:Indole Alkaloids; D010972:Platelet Activating Factor; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; C049985:staurosporine aglycone; D011464:Epoprostenol; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate