Effects of diadenosine triphosphate (Ap₃A) and diadenosine tetraphosphate (Ap₄A) on platelet aggregation in unfractionated human blood

Summary

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.