Potentiation by adrenaline of agonist-induced responses in normal human platelets in vitro

Adrenaline is not a true platelet agonist, but enhances aggregation, dense granule secretion, and phospholipase C induced by other agonists. In the present work we investigated the effect of adrenaline on other platelet responses. It strongly potentiated ADP-induced shape change in platelet-rich plasma, particularly when aggregation was prevented by EDTA. The degree of potentiation increased with increasing concentrations of ADP. Thrombin-induced α-granule secretion, measured by the release of fibrinogen in gel-filtered platelets, was also potentiated by adrenaline at thrombin concentrations above 0.05 U/ml. In contrast, adrenaline had little effect on thrombin-induced secretion of β-acetyl-hexosaminidase and potentiated very little liberation of arachidonate at high thrombin concentrations. When autocrine stimulation was inhibited by the removal of secreted ADP by creatine phosphate/creatine phosphate kinase and specific blocking of the thromboxane A(2) and fibrinogen receptors, the potentiation of thrombin-induced ADP + ATP secretion by adrenaline was reduced and this reduction was mostly due to the blocking of the thromboxane A(2) receptor. Protein tyrosine phosphorylation by both thrombin and collagen was reduced by adrenaline, and inhibitors of autocrine stimulation counteracted this reduction.