Platelet aggregation induced by simultaneous stimulation of the G_i and G_z pathways. (A) Aspirin-treated, washed human platelets were stimulated with 100 nM 2-MeSADP, 10 μM epinephrine, or a combination of both agonists, as noted. MRS2179 (100 μM), 100 nM AR-C69931MX, or 10 μM yohimbine, antagonizing P2Y₁, P2Y₁₂, and α_2A adrenergic receptor antagonists, respectively, were added 1 minute prior to platelet stimulation. All aggregation tracings were performed in the presence of 1 mg/mL fibrinogen. Tracings are representative of results obtained from 3 donors and 3 separate experiments. (B, C) Aspirin-treated, washed platelets were isolated from P2Y₁- or G_q-deficient mice as noted in “Materials and methods.” Samples were stimulated with either 3 μM ADP or 10 μM epinephrine at 37°C under stirring conditions (900 rpm). In the case where both ADP and epinephrine were added, the additions of the agonists were made simultaneously. All tracings are representative of data obtained from 3 separate experiments.