ADP receptor blockade inhibits NPP4/Ap3A-promoted platelet aggregation. The platelet ADP receptors, P2Y1 and P2Y12, were blocked using specific receptor antagonists (MRS 2179 and MRS 2395, respectively) in light transmission aggregometry experiments conducted in the presence of 50nM NPP4 and 80μM Ap3A. (A) Increasing concentrations of the P2Y1 receptor antagonist, MRS 2179, showed a dose-dependent inhibition of the platelet aggregation response in the presence of NPP4 and Ap3A. (B) Increasing concen-trations of the P2Y12 receptor antagonist, MRS 2395, showed a dose-dependent inhibition of the platelet aggregation response in the presence of NPP4 and Ap3A with complete inhibition by 200μM MRS 2395 (green curve). All experiments in this panel were conducted in the presence of 10% DMSO to ensure the solubility of MRS 2395. (C) ADP receptor inhibitors do not appreciably (≤ 4%) inhibit NPP4 enzymatic activity when added at 200-fold molar excess over NPP4 (100μM inhibitor to 5nM NPP4). All errors in measurement are less than 1% of the stated value.