Differences in the mode of action of 1-oleoyl-2-acetyl-glycerol and phorbol ester in platelet activation.
The ADP-hydrolyzing enzyme apyrase inhibited platelet aggregation and phosphorylation of a 40,000 dalton platelet protein (P40) induced by 1-oleoyl-2-acetyl glycerol (OAG), indicating a dependence on secreted ADP. Apyrase also enhanced OAG-induced potentiation of forskolin or prostaglandin I2 activation of cyclic AMP formation in platelets. Cyclic AMP formation induced by OAG alone could be demonstrated in the presence of a phosphodiesterase inhibitor. Elevation of cyclic AMP level inhibits platelet aggregation so that secreted ADP may be required to inhibit OAG-activated adenylate cyclase for aggregation to proceed. In contrast, apyrase only partially affected phosphorylation of P40 and aggregation induced by the tumor promoter 12-0-tetradecanoyl phorbol-13-acetate (TPA). TPA caused marked inhibition of forskolin-stimulated cyclic AMP formation. TPA inhibition of cyclic AMP formation was largely reversed by apyrase, indicating that it was mainly due to release of ADP.
D000262:Adenylyl Cyclases / Q000378:metabolism; D001081:Apyrase / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood*; D004075:Diglycerides / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010208:Papaverine / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001798:Blood Proteins; D004075:Diglycerides; D005989:Glycerides; D010704:Phorbols; D005576:Colforsin; C038237:1-oleoyl-2-acetylglycerol; D010208:Papaverine; D000242:Cyclic AMP; D001081:Apyrase; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate