FIG. 5.

Effects of pharmacological inhibitors of calpain-1 and PTP1B on platelet aggregation. Gel-filtered platelets were analyzed for platelet aggregation in response to synthetic inhibitors of calpains and PTP1B. The platelet aggregation was induced by 0.15 U/ml of thrombin. (A to E) WT platelets (A), WT platelets incubated with vehicle DMSO (B), and WT platelets incubated with the indicated concentrations of MDL (C to E). (F) Platelet aggregation response of calpain-1 null platelets. It is noteworthy that at 25 μM DMHV, although the final extent of platelet aggregation was not altered in calpain-1 null mice (G), the overall shape of the aggregation tracing without DMHV appears to be distinct (F). (H) The reduced platelet aggregation in calpain-1 null mice was rescued by incubation with 50 μM DMHV, a pharmacological inhibitor of tyrosine phosphatases, including PTP1B. (I) In the WT mouse platelets, 50 μM DMHV enhanced platelet aggregation at 0.075 U/ml thrombin activation. (J to L) Washed human platelets (2 × 10⁸/ml) were incubated with 25 μM and 50 μM DMHV for 30 min at room temperature for aggregation response to thrombin activation.