Effects of Diadenosine Triphosphate (Ap3A) and Diadenosine Tetraphosphate (Ap4A) on Platelet Aggregation in Unfractionated Human Blood

The effects on platelet aggregation of diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A), both of which are stored in and released from platelet granules, have been studied in unfractionated human blood using a microscopic platelet-count ratio method. Ap3A at submicromolar concentrations induces platelet aggregation whereas the homologue dinucleotide Ap4A has disaggregating potency. In the concentration range between 10(-7) to 10(-5) M, Ap3A has been found to be as effective as ADP in triggering aggregate formation. These results confirm and essentially extend our recent findings with platelet-rich plasma that Ap3A is able to trigger platelet aggregation by a slow release of ADP from Ap3A which is catalyzed by a plasma hydrolase. Formation of platelet aggregates was also followed kinetically using a turbidometric method which has been developed for this purpose. In contrast to ADP which very rapidly induces a transient state of aggregation, the effect of Ap3A occurs much more slowly but induces the same maximum of aggregation. The duration of the Ap3A stimulus, however, is longer than that of ADP pointing to a potential physiological function of Ap3A as a "masked" source for ADP.