title: Effects of protein kinase C activation on human platelet cyclic AMP metabolism.
abstract: Treatment of intact human platelets with the tumour-promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), specifically inhibited PGD2-induced cyclic AMP formation without affecting the regulation of cyclic AMP metabolism by PGI2, PGE1, 6-keto-PGE1, adenosine or adrenaline. This action of PMA was: (i) concentration-dependent; (ii) not mediated by evoked formation or release of endogenous regulators of adenylate cyclase activity (thromboxane A2 or ADP); (iii) mimicked by 1,2-dioctanoylglycerol (DiC8) but not by 4 alpha-phorbol 12,13-didecanoate (which does not activate protein kinase C); (iv) attenuated by Staurosporine. These results indicate that activation of protein kinase C in platelets may provide a regulatory mechanism to abrogate the effects of the endogenous adenylate cyclase stimulant PGD2 without compromising the effects of exogenous stimulants of adenylate cyclase (PGI2, 6-keto-PGE1, adenosine).
authors.affiliation: Department of Pharmacology, University of Glasgow, Scotland.
authors.forename: M
authors.initials: M
authors.lastname: Bushfield
authors.forename: S L
authors.initials: SL
authors.lastname: Hopple
authors.forename: I F
authors.initials: IF
authors.lastname: Gibson
authors.forename: F A
authors.initials: FA
authors.lastname: Murdoch
authors.forename: D E
authors.initials: DE
authors.lastname: MacIntyre
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000097:blood; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D000242:Cyclic AMP / Q000097:blood*; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D011493:Protein Kinase C / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D011457:Prostaglandins D; D000244:Adenosine Diphosphate; C022950:6-ketoprostaglandin E1; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2; D004837:Epinephrine