Continuous proteolysis resulting in consumption of major cytoskeletal proteins may be essential for platelet activation and aggregation. In this study we evaluated the effect of a known protease inhibitor, Leupeptin, on agonist induced @entity1423 and secretion. Platelets exposed to 10 ugs/ml of Leupeptin did not aggregate in response to the action of @entity556 (0.2 u/ml). However, a concentration of Leupeptin as high as 250 ugs/ml did not prevent @entity3899 induced aggregation and secretion. Leupeptin (100 ugs/ml) effectively blocked @entity556 (0.2 u/ml) induced elevation of cytosolic @entity460 , but did not affect @entity3899 induced elevation of platelet intracellular @entity460 levels. At a concentration of 100 ug/ml, Leupeptin effectively blocked @entity556 (0.5 u/ml) induced clot formation of platelet poor plasma, suggesting that it can exert its effect on @entity556 by preventing fibrinogen degradation. Effective Ki for the competitive inhibition of @entity556 induced hydrolysis of a chromogenic substrate, @entity3613 , by Leupeptin was 2.4 uM. Leupeptin inhibition of platelet function was reversible by washing platelets free of the polypeptide. Results of our study demonstrate that Leupeptin inhibits @entity556 induced platelet activation, probably by interfering with its proteolytic activity on the platelet surface membrane. However, inhibition of platelet surface membrane associated proteases did not prevent activation of platelets by other agonists.

Influence of a XXXX dependent protease inhibitor on platelet activation and secretion.

@entity556 :: ('2147', 'Gene') :: ['thrombin'] @entity1423 :: ('MESH:D001791', 'Disease') :: ['platelet aggregation'] @entity3613 :: ('MESH:C021129', 'Chemical') :: ['S2238'] @entity3899 :: ('CHEBI:32395', 'Chemical') :: ['arachidonate'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium']
@entity460 :: (MESH:D002118,Chemical) :: ['calcium']
