Calpains are involved in phosphatidylinositol 3',4'-bisphosphate synthesis dependent on the alpha IIb beta 3 integrin engagement in thrombin-stimulated platelets

In thrombin-stimulated platelets αIIbβ3 integrin engagement triggers both phosphatidylinositol 3′,4′-bisphosphate synthesis and calpain activation. We checked the possible involvement of calpains in phosphatidylinositol 3-kinase signalling pathway using a cell permeant specific inhibitor of calpains, calpeptin. In conditions where thrombin-induced platelet aggregation and secretion were not impaired, we found a dose-dependent inhibition of phosphatidylinositol 3,4-bisphosphate synthesis by calpeptin from 50 μg/ml. Moreover, pretreatment of platelets by both calpeptin and the peptide RGDS, an inhibitor of fibrinogen binding to activated αIIbβ3 integrin, did not induce additive effects on phosphatidylinositol 3,4-bisphosphate inhibition. Finally, the p85 regulatory subunit of phosphatidylinositol 3-kinase was still translocated to the cytoskeleton in calpeptin-treated platelets. These data indicate that calpains are involved in the regulation of αIIbβ3 integrin-dependent phosphatidylinositol 3-kinase signalling pathway.©1997 Federation of European Biochemical Societies.