Figure 1.
Effect of GIRK channel blockers on ADP-induced platelet aggregation, TXA2 generation, and dense granule secretion in non–aspirin-treated human platelets. Washed non–aspirin-treated human platelets (A-B,D-G) or aspirin-treated human platelets (C) were stimulated with ADP (10 μM) (A-F) or 2MeSADP (100 nM) (G) for 3.5 minutes under stirring conditions at 37°C in the presence and absence of different concentrations of SCH23390, or U50488H. Fibrinogen (1 mg/mL) was added to all the samples prior to the addition of the agonist. In panels A, B, and C, platelet aggregation was measured by measuring light transmittance. In panels D and F, and G, TXB2 levels were analyzed as described in “Materials and methods.” In panel E, ATP secretion was measured as described in “Materials and methods.” In panels D and E, different concentrations of SCH23390 or U50488H were used as indicated. In panels F and G, 10-μM concentrations of SCH23390, U50488H, or SKF38393 were used. The data are represented as percent maximal TXB2 generated by ADP or 2MeSADP in the absence of antagonists. Each bar is the average of 3 experiments ± SEM from 3 different donors.