Adenine nucleotide metabolism of blood platelets: IV. Platelet aggregation response to exogenous ATP and ADP

Abstract

1. 1. The effect of [ 14C 10]ADP and [ 14C 10]ATP on aggregation and disaggregation of human platelets, measured by changes in light absorption was investigated simultaneously with the metabolism of these labelled compounds in plasma. 2. 2. Platelets incubated with ADP lost their ability to aggregate on addition of more ADP. This loss of aggregability was not due to adenosine formation, but appeared to be the result of exposure to ADP and it is suggested that the platelets become refractory. 3. 3. ATP induced loss of aggregation partly through a refractory state and partly through platelet uptake of adenosine formed during ATP degradation. 4. 4. Platelet disaggregation after ADP-induced aggregation remained the same when adenosine formation was prevented by exogenous adenosine deaminase. It also correlated poorly with the slow ADP degradation in the system. 5. 5. Suitable concentrations of potato apyrase added to platelet-rich plasma during ADP-induced platelet aggregation rapidly cleared the ADP and produced accelerated and complete dispersal of the platelet aggregates. 6. 6. The suggestion is made that some platelets in plasma are refractory when ADP is first added to induce aggregation, but respond later. The observed pattern of ADP-induced platelet aggregation and disaggregation is then a balance between aggregating platelets becoming refractory and refractory platelets becoming responsive again.