Possible mechanisms of the potentiation of blood-platelet activation by adrenaline.
Vasopressin and adrenaline in combination exert synergistic effects on platelet activity. This study investigated the effects of sub-threshold concentrations of adrenaline (0.1-1 microM) on vasopressin (10 nM-1 microM)-induced platelet aggregation, ATP secretion, elevation of cytosolic free Ca2+ concentration ([Ca2+]i) and hydrolysis of inositol phospholipids, monitored as [32P]phosphatidic acid formation. Potentiation of vasopressin-induced aggregation and ATP secretion by adrenaline was accompanied by enhanced elevation of [Ca2+]i and [32P]phosphatidic acid formation. The stimulatory effects of adrenaline on vasopressin-induced platelet activation were mimicked by the combination of the Ca2+ ionophore, ionomycin, and the protein kinase C activator, phorbol 12-myristate 13-acetate, but not by either of these agents alone. These results suggest that the potentiation of vasopressin-induced platelet activation by adrenaline is mediated via enhancement of inositol phospholipid hydrolysis and elevation of [Ca2+]i.
D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D015759:Ionomycin; D010712:Phosphatidic Acids / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D004987:Ethers; D010712:Phosphatidic Acids; D014667:Vasopressins; D015759:Ionomycin; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004837:Epinephrine