Potential participation of calpain in platelet activation studied by use of a cell penetrating calpain inhibitor (calpeptin) |
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Authors: | T Tsujinaka H Ariyoshi Y Uemura M Sakon J Kambayashi T Mori |
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Institution: | Second Department of Surgery, Osaka University Medical School, Japan. |
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Abstract: | Employing a cell penetrating calpain inhibitor (calpeptin), the role of calpain in platelet activation was examined. In washed platelets (WPs) both thrombin and collagen-induced platelet aggregation were dose-dependently inhibited by calpeptin. The addition of plasma to WPs interfered with the action of calpeptin, however more than 3 min preincubation of calpeptin with WPs completely abolished the influence of plasma. In thrombin-activated WPs with calcium, the increase of intracellular calcium concentration, Ca2+]i, and the production of inositol triphosphate (IP3) were dose-dependently inhibited by calpeptin. The generation of thromboxane B2 (TxB2) was inhibited by calpeptin in collagen and thrombin-activated WPs. In 3H]-arachidonic acid (AA)-labelled platelets, calpeptin increased the amount of 3H]-AA liberated by inhibiting 3H]-AA degradation after collagen or thrombin stimulation. When 14C]-AA degradation by the platelet suspension was observed, calpeptin inhibited TxB2 and hydroxyheptadecatrienoic acid (HHT) generation but increased prostaglandin (PG) E1, E2, 12-hydroxyeicosatetraenoic acid (12HETE) and AA. Based on these findings, calpain may be involved in the activation phospholipase C and thromboxane synthetase. |
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