Effects of the P2‐purinoceptor antagonist, suramin, on human platelet aggregation induced by adenosine 5′‐diphosphate

Abstract

1 The effects of suramin, a trypanocidal drug which has been reported to be a P₂-purinoceptor antagonist on smooth muscle, were investigated in human platelets, where adenosine 5′-diphosphate (ADP) induces aggregation by acting on a subtype of purinoceptors which has been called P_2T. 2 Suramin (100 μm) had no inhibitory effect on ADP-induced platelet aggregation in plasma, even after 40 min incubation in the presence of bacitracin, a peptidase inhibitor, and did not affect the ability of adenosine 5′-triphosphate (ATP) (40 μm) to inhibit competitively ADP-induced aggregation. This lack of effect of suramin on platelets in plasma is probably due to its extensive binding to plasma proteins. 3 In washed platelets, suramin (50–400 μm) acted as an apparently competitive antagonist, causing parallel shifts to the right of the log concentration-response curve to ADP. No depression of the maximal response to ADP was observed at concentrations of suramin (50–150 μm) for which full log concentration-response curves to ADP could be obtained, but the slope of the Schild plot was around 2, indicating that this antagonism was not simply competitive. The apparent pA₂ value for suramin, taken from this Schild plot, was 4.6. 4 Suramin (200–400 μm) also noncompetitively inhibited aggregation induced by U46619 (a thromboxane receptor agonist) or by 5-hydroxytryptamine in the presence of adrenaline (100 μm), and caused a depression of the maximal response to these agonists. This nonspecific effect of suramin may explain the high Schild plot slope obtained against ADP. 5 These results provide evidence that the ADP receptor on human platelets is indeed similar to the P₂-purinoceptors responding to adenine nucleotides on smooth muscle and other tissues, and show that suramin cannot distinguish between the proposed subtypes of the P₂-purinoceptors.