The effect of kinase inhibitors on platelet aggregation caused by the simultaneous stimulation of Gi and Gz or Gq and Gi pathways. Platelets were preincubated with kinase inhibitors as follows: 10 minutes at 37°C with dimethyl sulfoxide (DMSO) (vehicle), 3 minutes at 37°C with 10 μM Ro 31-8220, 10 minutes of preincubation at 37°C with 1 μM dimethyl BAPTA-AM, or 10 minutes of preincubation with 25 μM LY294002. Platelets were stimulated with 100 nM 2-MeSADP, 10 μM epinephrine, or a combination of both agonists, as noted, for Gi and Gz stimulation. MRS2179 (100 μM) was added 1 minute prior to platelet stimulation. ADP (10 μM) was used as an agonist for stimulation of Gq and Gi pathways. 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.
