cathepsin-g and defibrotide

cathepsin-g has been researched along with defibrotide* in 2 studies

Other Studies

2 other study(ies) available for cathepsin-g and defibrotide

ArticleYear
Endothelium-dependent relaxation induced by cathepsin G in porcine pulmonary arteries.
    British journal of pharmacology, 2001, Volume: 133, Issue:3

    Serine proteinases elicit profound cellular effects in various tissues mediated by activation of proteinase-activated receptors (PAR). In the present study, we investigated the vascular effects of cathepsin G, a serine proteinase that is present in the azurophil granules of leukocytes and is known to activate several cells that express PARs. In prostaglandin F2alpha (3 microM)-precontracted rings from porcine pulmonary arteries with intact endothelium, cathepsin G caused concentration-dependent relaxant responses (pEC(50)=9.64+/-0.12). The endothelium-dependent relaxant effect of cathepsin G could also be demonstrated in porcine coronary arteries (pEC(50)=9.23+/-0.07). In pulmonary arteries the cathepsin G-induced relaxation was inhibited after blockade of nitric oxide synthesis by L-NAME (200 microM) and was absent in endothelium-denuded vessels. Bradykinin- and cathepsin G-induced relaxant effects were associated with a 5.7 fold and 2.4 fold increase in the concentration of cyclic GMP, respectively. Compared with thrombin and trypsin, which also produced an endothelium-dependent relaxation in pulmonary arteries, cathepsin G was 2.5 and four times more potent, respectively. Cathepsin G caused only small homologous desensitization. In cathepsin G-challenged vessels, thrombin was still able to elicit a relaxant effect. The effects of cathepsin G were blocked by soybean trypsin inhibitor (IC(50)=0.043 microg ml(-1)), suggesting that proteolytic activity is essential for induction of relaxation. Recombinant acetyl-eglin C proved to be a potent inhibitor (IC(50)=0.14 microg ml(-1)) of the cathepsin G effect, whereas neither indomethacin (3 microM) nor the thrombin inhibitor hirudin (5 ATU ml(-1)) elicited any inhibitory activity. Due to their polyanionic structure defibrotide (IC(50)=0.11 microg ml(-1)), heparin (IC(50)=0.48 microg ml(-1)) and suramin (IC(50)=1.85 microg ml(-1)) diminished significantly the relaxation in response to the basic protein cathepsin G. In conclusion, like thrombin and trypsin, cathepsin G is able to induce endothelium-dependent vascular relaxation. It can be released from activated leukocytes at sites of vascular injury and inflammation and, therefore, sufficiently high concentrations might be reached locally in the vascular space to induce vasodilatation.

    Topics: Animals; Bradykinin; Cathepsin G; Cathepsins; Cyclic GMP; Dinoprost; Endothelium, Vascular; Heparin; Humans; Inhibitory Concentration 50; NG-Nitroarginine Methyl Ester; Polydeoxyribonucleotides; Proteins; Pulmonary Artery; Serine Endopeptidases; Serine Proteinase Inhibitors; Serpins; Suramin; Swine; Thrombin; Trypsin; Vasodilation

2001
Defibrotide inhibits platelet activation by cathepsin G released from stimulated polymorphonuclear leukocytes.
    Thrombosis and haemostasis, 1992, Jun-01, Volume: 67, Issue:6

    Defibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

    Topics: Catalysis; Cathepsin G; Cathepsins; Fibrinolytic Agents; Humans; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Platelet Activation; Polydeoxyribonucleotides; Serine Endopeptidases; Serotonin; Thrombin; Thromboxane B2

1992