EVIDENCE THAT ADENOSINE-DIPHOSPHATE CAN ACTIVATE ADENYLATE-CYCLASE VIA CONVERSION TO ADENOSINE IN PLATELET-RICH PLASMA CONTAINING MAGNESIUM

When adenosine diphosphate (ADP) is added to hirudinized platelet-rich plasma (PRP) in which the level of platelet cAMP has been pharmacolog ically elevated, there is an initial rapid fall in the level of cAMP b rought about by inhibition of adenylate cyclase. This may be followed by a subsequent activation of adenylate cyclase that does not occur wh en citrated PRP is used in place of hirudinized PRP, and is more prono unced in the presence of added Mg2+. Here we provide evidence that a) the Mg2+-dependent activation of adenylate cyclase seen in hirudinized PRP is mediated by adenosine, b) the adenosine produced synergizes wi th forskolin and with DN9693 to raise the level of cAMP in platelets, but not with iloprost, c) Mg2+ does not influence directly the rate or extent of cAMP production and so is more likely to influence the rate of adenosine production, and d) activation of adenylate cyclase by ad enosine can lead to inhibition of platelet aggregation. ARL 66096, a P -2T purinoceptor antagonist which inhibits ADP induced platelet aggreg ation, prevented inhibition of adenylate cyclase by ADP. Conversely, A RL 66096 did not appear to inhibit conversion of ADP to adenosine and subsequent activation of adenylate cyclase.