Regulation of cyclic AMP levels and aggregation in human platelets by prostaglandin E .

Abstract

Abstract Cyclic AMP levels in citrated platelet-rich plasma (PRP) were determined during the course of platelet aggregation induced by ADP, adrenalin, or collagen. Studies were performed in the presence and absence of the aggregation inhibitor prostaglandin E 1 (PGE 1 ). Aggregating agents had no consistent effect on basal cyclic AMP concentration. When preincubation with PGE 1 had resulted in increases in cyclic AMP concentration, the addition of ADP, collagen, or adrenalin resulted in a prompt reduction to basal levels. However, this response need not indicate that a lowering of cyclic AMP levels is essential for aggregation to occur. Inhibition of platelet aggregation by PGE 1 appeared to be mediated by increases in cyclic AMP, and the strength of inhibition for a given concentration of aggregating agent was related to the size of the increase. The maximal effect of PGE 1 on aggregation lagged behind the maximal increase in cyclic AMP and persisted after cyclic AMP levels had declined markedly. Reversal of ADP-induced aggregation by PGE 1 also appeared to be mediated by increased platelet cyclic AMP. When the cyclic AMP level of platelets deaggregated by PGE 1 declined, reaggregation did not occur. These observations suggest that cyclic AMP is not a direct inhibitor of the action of aggregating agents on platelets. Increase in cyclic AMP appears to trigger a mechanism which results in a relatively stable inhibitory effect on platelet function.