Diadenosine triphosphate (Ap3A) mediates human platelet aggregation by liberation of ADP

Human platelets store considerable amounts of diadenosine 51,5111-P1, P3-triphosphate, which is released together with the homologue diadenosine tetraphosphate (Ap4A) upon thrombin-induced aggregation (Lüthje,J. & Ogilvie,A. (1983) Biochem. Biophys. Res. Commun. 115, 253-260). We now report that, when added to platelet-rich plasma at 10-20 micron, diadenosine triphosphate gradually induces aggregation. The addition of diadenosine tetraphosphate antagonizes this effect by rapidly disaggregating the platelets. When another physiological but structurally unrelated stimulus, i.e. PAF (Platelet activating factor) is introduced into the system, diadenosine triphosphate drastically enhances and prolongs the aggregatory effect of PAF. Again, Ap4A is antagonistic in this system. The mechanism of Ap3A-stimulation can be explained by the slow and continuous liberation of ADP from Ap3A by the action of a hydrolyzing enzyme which is present in human plasma. Our studies suggest that Ap3A may be physiologically important in providing a relatively long-lived stimulus that can modulate platelet aggregation.