ATP- and ADP-Induced Rat Platelet Aggregation: Significance of Plasma in ATP-Induced Aggregation^[*]

Summary

ATP caused platelet aggregation in rat platelet-rich plasma (PRP) but in contrast strongly inhibited ADP-induced human platelet aggregation. ADP-induced aggregation of rat platelets suspended in human plasma was strongly inhibited by ATP, whereas human platelets in rat plasma were aggregated by ADP. The ATP analog β,γ-methylene ATP which is not dephosphorylated did not induce aggregation in rat PRP. Adenosine, AMP, 2- chloroadenosine, α,β-methylene ADP and β,γ-methylene ATP each inhibited ATP-induced aggregation of platelets in rat PRP to a similar extent as ADP-induced aggregation. A solution containing creatine kinase and creatine phosphate (which converts ADP to ATP) rapidly reversed both ADP- and ATP-induced aggregation in rat PRP; preincubation with this solution completely inhibited rat platelet aggregation induced by both ADP and ATP. Adenosine-8-¹⁴C-triphosphate ([¹⁴C]-ATP) conversion to [¹⁴C]-ADP was about five-fold faster in rat plasma than in human plasma. Addition of creatine phosphate to rat PRP strongly inhibited ATP-induced aggregation, while creatine or creatine kinase slightly potentiated aggregation by ATP. Creatine phosphate, creatine, or creatine kinase individually had minimal and varying effects on ADP-induced rat platelet aggregation. These results suggest that the observed phenomenon of ATP-induced aggregation in rat PRP is caused by a higher activity of creatine kinase in rat plasma than in human plasma, which converts the added ATP to ADP, a potent aggregator.

^* Supported by USPHS Grant CA 07340

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