Synergistic potentiation by epinephrine of collagen or thrombin-induced calcium mobilization in human platelets

Abstract

Changes in cytoplasmic free calcium in response to epinephrine in combination with other agonists were studied in human platelets loaded with the fluorescent calcium indicator, quin 2. In the presence of 1mM external calcium, epinephrine augmented the increase in cytoplasmic free calcium in response to collagen or thrombin, and this was inhibited by yohimbine. In the absence of extracellular calcium, thrombin and collagen only caused a small increase in cytoplasmic free calcium, and the response was not enhanced by epinephrine. High concentrations of epinephrine alone caused a small increase in cytoplasmic free calcium in platelets when calcium was present externally. Inhibition of cyclooxygenase by aspirin markedly reduced the calcium response to collagen and almost completely inhibited potentiation by epinephrine. The calcium response to thrombin was inhibited to a lesser extent by aspirin, and aspirin did not prevent potentiation by epinephrine. These findings suggest that augmentation of the cytoplasmic free calcium level may be involved in the potentiation of platelet responses to agonists by epinephrine, and that metabolites of arachidonic acid make an important contribution to this action of epinephrine.