Epinephrine potentiates human platelet activation but is not an aggregating agent.
Epinephrine can in certain in vitro conditions induce the aggregation of human platelets and could play an important role in vivo in the appearance of thrombotic disorders when catecholamine levels are increased. This study examines some functional and biochemical responses to epinephrine. Epinephrine induces the aggregation and serotonin secretion of human platelets in citrated plasma. This is not due to a direct effect of citrate itself, such as the lowering of plasma free Ca2+ but more likely to the generation of traces of thrombin during blood collection, as suggested by abrogation of these platelet responses when hirudin was added before citrate. When washed human platelets suspended in Tyrode buffer containing 2 mM Ca2+, 0.35% albumin and apyrase, and 0.1-100 microM epinephrine were used, no shape change, aggregation, or secretion of serotonin was observed, nor was the platelet ultrastructure modified. Epinephrine does not modify platelet membrane fluidity, as studied with the lipophilic fluorescent probe trimethylammonium-diphenylhexatriene. It has no direct effect on fibrinogen binding to intact platelets, intracellular Ca2+ levels measured by quin2, or protein phosphorylation. Epinephrine potentiates the action of all types of aggregating agents on aggregation, secretion, intracellular Ca2+ levels, membrane fluidity, fibrinogen binding, or protein phosphorylation. These effects are mediated by alpha 2-adrenergic agonists and inhibited by alpha 2-adrenergic antagonists. This study shows that epinephrine alone does not induce modifications of morphology, metabolism, or function of intact and functional washed human platelets and that it cannot be considered per se as an aggregating agent. However, epinephrine interacts with alpha 2-adrenergic receptors on human platelets and potentiates biochemical and aggregatory responses induced by other platelet agonists.
Lanza
F
F
Institut National de la Santé et de la Recherche Médicale U311, Centre Régional de Transfusion Sanguine, Strasbourg, France.
Beretz
A
A
Stierlé
A
A
Hanau
D
D
Kubina
M
M
Cazenave
J P
JP
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism; D002118:Calcium / Q000097:blood; D003593:Cytoplasm / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D012701:Serotonin / Q000097:blood / Q000378:metabolism; D013917:Thrombin / Q000502:physiology
D001798:Blood Proteins; D012701:Serotonin; D000244:Adenosine Diphosphate; D013917:Thrombin; D002118:Calcium; D004837:Epinephrine