Phorbol ester stimulates PAF synthesis via the activation of protein kinase C in rat leukocytes.
When rat pleural mononuclear leukocytes were stimulated with 1 microM phorbol myristate acetate (PMA), platelet-activating factor (PAF)-like activity was detected in the supernatant and the cellular fractions of the incubation mixture, as measured by rabbit platelet aggregation. C16PAF activity peaked at 30 min in both fractions. Acetyltransferase activity in the microsomal fraction of the stimulated cells also increased rapidly and showed a peak at 10 min. A protein kinase C inhibitor, staurosporine, and an inhibitor of phospholipase A2, p-bromophen-acylbromide, inhibited stimulated PAF formation in both fractions. Staurosporine also inhibited PMA induced acetyltransferase activity. The data suggest that PMA stimulates PAF synthesis by the remodeling pathway in rat pleural cells through activation of both phospholipase A2 and acetyltransferase, and that the acetyltransferase, in turn, may be activated through activation of protein kinase C.
Hayashi
M
M
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Imai
Y
Y
Oh-ishi
S
S
D000123:Acetyltransferases / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010972:Platelet Activating Factor / Q000096:biosynthesis* / Q000302:isolation & purification / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D010972:Platelet Activating Factor; D000123:Acetyltransferases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate