Independent Induction of Platelet Aggregation and Secretion by Prostaglandin Endoperoxide Analogues and Thromboxane A2-Like Material
We have investigated the mechanims of platelet activation by two prostaglandin endoperoxide analogues (U-46619 and U-44069) using a new instrument that simultaneously monitors platelet aggregation and secretion. Low concentrations of these compounds induce platelet aggregation without secretion (i. e., primary aggregation), while slightly higher concentrations induce biphasic aggregation with secretion paralleling the second phase. At still higher concentrations, aggregation and secretion begin simultaneously, and in the absence of stirring there is secretion but no aggregation. A critical concentration of endoperoxide analogues can often be found that will induce 2 waves of secretion, a phenomenon not seen with other stimuli. Similar results were obtained with thromboxane A2-like material that was generated by incubation of dog platelets with Na-arachidonate. In contrast, when platelets are stimulated with Na-arachidonate, the precursor of the endoperoxides and thromboxanes, we never observe significant aggregation without secretion, and even at the lowest concentrations secretion is independent of aggregation. We conclude that both the prostaglandin endoperoxide analogues and thromboxane A2-like material induce platelet aggregation independent of released ADP and only at higher concentrations can directly induce secretion, whereas Na-arachidonate induces aggregation and secretion in parallel.