Antiplatelet Action of Adenosine

Wide variations in response to aggregating agents and their inhibition by adenosine have been reported in blood samples of various species (28,35,36). Adenosine (10-100 pM) inhibits ADP-induced platelet aggregation in PRP samples from human, rabbit, dog (37,38) and sheep (39), whereas adenosine is non-inhibitory of platelet aggregation in PRP from guinea-pig, horse, rat or cat blood (37,38). In mouse PRP, adenosine (10-1000 pM) inhibits only 33% of submaximal ADP (1 pM)-induced platelet aggregation (40). The data from these studies are summarized in Table 1. 

The mechanism for non-inhibitory action of adenosine in guinea-pig, horse, cat and rat blood is not well understood, although their platelets aggregate normally with ADP (28,35,36,41). Adenosine-mediated increases in intracellular cAMP levels were similar in rat and human platelets, however adenosine shows no inhibition of platelet aggregation in rat PRP (42,43). It has been suggested that the difference in the inhibitory effectiveness of adenosine on rat and human platelets is quantitative rather than qualitative and apparently depended on the inability of adenosine to increase intracellular cAMP sufficiently in rat platelets (42). 

Interestingly, human platelets resuspended in rat plasma retain adenosine inhibition of ADP-induced aggregation, whereas rat platelets resuspended in human plasma behave like rat PRP, suggesting that the non-inhibitory effect of adenosine in rat PRP is an intrinsic 

Agonists ECj0 values (piM) Platelet aggregation (%) 5-HT release Ref.  

Ado-depleted PRP PRP was treated with adenosine deaminase (ADA 2 units/ml) to degrade plasma adenosine. 

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Dawicki, DD, Aganval, KC, Parks, RE, Jr, Potentiation ofthe antiplatelet action of adenosine in whole blood by dipyridamole or dilazep and the cAMP phosphodiesterase inhibitor, RA-233, Thromb. Res, 1986,43 161-175. 

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