Effects of thrombin, phorbol myristate acetate and prostaglandin D2 on 40-41 kDa protein that is ADP ribosylated by pertussis toxin in platelets.
Intact platelets were stimulated with thrombin and the amount of GTP-binding protein (G-protein) oligomers was assessed by measuring ADP ribosylation of 40-41 kDa protein by pertussis toxin in isolated membranes. The toxin substrate fell by 57-62% in 10-60 s, but then returned towards normal over 5 min. Recovery was greatly enhanced by removal of thrombin from receptors with hirudin. Phorbol myristate acetate increased ADP-ribosylatable protein, but only back to initial levels prior to PMA. In contrast prostaglandin D2 plus theophylline (which increase cyclic AMP) did not increase ADP ribosylation, but could completely block the fall of the toxin substrate caused by thrombin. These results indicate that activation of thrombin receptors promotes the dissociation of G-protein oligomers to release free alpha-subunits, and this effect can be modulated by protein kinase C and cyclic AMP-dependent protein kinase. The possible relationships of these findings to the regulation of stimulus-response coupling in platelets is discussed.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D037342:Pertussis Toxin; D010704:Phorbols / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects; D018179:Receptors, Thrombin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D006023:Glycoproteins; D006629:Hirudins; D008565:Membrane Proteins; D010704:Phorbols; D010980:Platelet Membrane Glycoproteins; D011457:Prostaglandins D; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D037342:Pertussis Toxin; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D015230:Prostaglandin D2