Adenine nucleotide metabolism of blood platelets: II. Uptake of adenosine and inhibition of ADP-induced platelet aggregation

Abstract

1. 1. Inhibition of ADP-induced aggregation of human platelets in plasma by AMP, adenosine monoacetate and adenosine monopropionate has been studied. These compounds produced inhibition only after hydrolysis to adenosine in plasma. 2. 2. The concentration of adenosine in plasma and the amount phosphorylated in the platelets during inhibition of aggregation was estimated by use of [ 14C 10]adenosine and [ 14C 10]AMP. Inhibition correlated well with the rate of phosphorylation, but poorly with the adenosine concentration. 3. 3. Inhibition of platelet aggregation remained present after rapid clearance of the adenosine from plasma on addition of adenosine deaminase. 4. 4. Rising concentrations of adenosine did not induce 100 % inhibition of aggregation. Both inhibition and the rate of phosphorylation were saturated at the same adenosine concentration. 5. 5. d-2-Deoxyglucose and antimycin together strongly inhibited ADP-induced platelet aggregation, reduced adenosine phosphorylation by 50 % and conversion of [8- 14C]adenine to nucleotides by 80 %. 6. 6. These results suggest that adenosine is transported across the membrane and perhaps phosphorylated before inducing inhibition. Inhibition might be caused by competition for energy required for both platelet aggregation and the adenosine transport—phosphorylation process.