We have prepared a nonagglutinating derivative of wheat germ agglutinin by cyanogen bromide treatment of the lectin and used it as a probe to study the thrombin-platelet interaction. The lectin derivative inhibited platelet aggregation by thrombin while aggregation induced by collagen. ristocetin, adenosine diphosphate. wheat germ agglutinin, or trypsin was not significantly affected. Under sim...

The tumor-promoting phorbol diester 4 beta-phorbol 12-myristate 13-acetate (PMA) inhibited mobilization of intracellular Ca2+ in platelets by thrombin (also trypsin and 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphocholine). PMA was effective over the same concentration range that activates protein kinase C in intact platelets; IC50 vs. thrombin = 2 ng/ml, 3.4 nM: greater than 90% inhibition at 10-20...

We investigated the mechanisms by which elevated intracellular cAMP concentration inhibits the thrombin-induced ICAM-1 expression in endothelial cells. Exposure of human umbilical vein endothelial cells to forskolin or dibutyryl cAMP, which increase intracellular cAMP by separate mechanisms, inhibited the thrombin-induced ICAM-1 expression. This effect of cAMP was secondary to inhibition of NF-...

Thrombin is a plasma serine protease that plays a key role in coagulation and hemostasis but also in thromboembolic diseases. Direct thrombin inhibitors could be beneficial for future anticoagulant therapy in the prophylaxis of venous and arterial thrombosis as well as myocardial infarction. To design the efficient thrombin inhibitors we have synthesized and studied peptide-based inhibitors res...

Activation of coagulation and vascular inflammation are prominent features of sickle cell disease (SCD). Previously, we have shown that inhibition of tissue factor (TF) attenuates activation of coagulation and vascular inflammation in mouse models of SCD. In this study, we examined the mechanism by which coagulation proteases enhance vascular inflammation in sickle BERK mice. To specifically in...

In this study we show that high molecular weight kininogen (HK) inhibited alpha-thrombin-induced aggregation of human platelets in a dose-dependent manner with complete inhibition occurring at plasma concentration (0.67 mumol/L) of HK. HK (0.67 mumol/L) also completely inhibited thrombin-induced cleavage of aggregin (Mr = 100 Kd), a surface membrane protein that mediates adenosine diphosphate (...

BACKGROUND Optimal coronary thrombolysis should be prompt and persistent. Although activation of platelets and increased thrombin activity have been associated with clinical thrombolysis, the role of each in delaying thrombolysis or inducing early coronary reocclusion has been difficult to define. METHODS AND RESULTS In conscious dogs with coronary thrombosis induced by electrical current, we...

Heparin fractions of different molecular weight and with high affinity for antithrombin were studied with respect to their ability to potentiate the inhibition of activated clotting factors by antithrombin. Inhibition of thrombin, Factor IXa and Factor XIa showed similarities in the dependence on the molecular weight of heparin and was found to decrease with decreasing molecular weight. Inactiv...