DIFFERENTIAL INHIBITION BY ADENOSINE OR BY PROSTAGLANDIN E 1 OF HUMAN PLATELET AGGREGATION INDUCED BY ADENOSINE 5′‐O‐(1‐THIODIPHOSPHATE) AND ADENOSINE 5′‐O‐(2‐THIODIPHOSPHATE)

Adenosine 5′‐diphosphate (ADP) induces human platelet aggregation and inhibits stimulated adenylate cyclase. Adenosine 5′‐O‐(1‐thiodiphosphate) (ADP‐α‐S) and adenosine 5′‐O‐(2‐thiodiphosphate) (ADP‐β‐S) act at the ADP receptor and achieve the same maximal rate of human platelet aggregation as each other. Adenosine and prostaglandin E 1 , which noncompetitively inhibit ADP‐induced aggregation by stimulating adenylate cyclase, inhibit aggregation induced by ADP‐α‐S more than aggregation induced by ADP‐β‐S. ADP‐α‐S, unlike ADP‐β‐S and ADP itself, does not inhibit stimulated adenylate cyclase. This suggests that the inhibition of stimulated adenylate cyclase by ADP, although not a cause of aggregation, may be of physiological importance in reducing the effects of endogenous agents such as adenosine and prostaglandins (for example, prostacyclin) to which the platelet may be exposed. Although the inhibition by ADP of adenylate cyclase cannot be the cause of aggregation, it could limit the inhibitory effects of agents such as PGE 1 and adenosine which activate adenylate cyclase. The observation that PGE 1 and adenosine are more powerful inhibitors of aggregation induced by vasopressin than by ADP (Haslam & Rosson, 1972), is consistent with this suggestion, although ADP and vasopressin do not act at the same receptor (Macfarlane & Mills, 1975). The differential effects on adenylate cyclase of ADP‐α‐S and ADP‐β‐S, which both act at the ADP receptor (Cusack & Hourani, 1981a,b), provides the first opportunity to investigate whether inhibition of adenylate cyclase by ADP receptor agonists can limit the effects on aggregation of inhibitors such as adenosine and PGE 1 .