The disappearance of adenosine from blood and platelet suspension in relation to the platelet cyclic AMP content

Abstract

Adenosine exerts anti-aggregatory effects on human platelets in vitro, probably by increasing intraplatelet levels of cyclic AMP. In addition, adenosine prevents platelet loss in vivo. We have studied the relationship between the concentration of adenosine in the platelet media and the level of cAMP. In PRP, exogenous adenosine (2-16 microM) was eliminated with a half-life close to 5 min. Approximately half of the added adenosine was deaminated (blocked by 1-2 microM EHNA), and half was eliminated by uptake into platelets (blocked by 2 microM dipyridamole). In whole blood the half-life for adenosine was much shorter, about 15 s. Addition of adenosine deaminase (0.3 microgram ml-1) to PRP resulted in a measured half-life for adenosine approximating that of whole blood. In PRP where adenosine was eliminated as quickly as in whole blood, the adenosine-mediated stimulation of cAMP was 35% lower than in PRP, and the cAMP response lasted 2 min versus 15 min in normal PRP. These results suggest that the magnitude and duration of adenosine's effect on platelets are markedly overestimated by studying platelet suspensions. In blood, the effect of adenosine is smaller in magnitude and very transient. The possibility is discussed that the action of adenosine in vivo on blood platelets can therefore be quite local.