In vitro interaction of C1-inhibitor with thrombin.

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Cugno M, Bos I, Lubbers Y, Hack CE, Agostoni A

In vitro interaction of C1-inhibitor with thrombin.

Blood Coagul Fibrinolysis. 2001 Jun;12(4):253-60.

PubMed ID

11460008 [ View in PubMed

]

Abstract

Previous observations of increased generation of thrombin during acute attacks of angioedema in plasma of patients with C1-inhibitor (C1-INH) deficiency prompted us to evaluate the interaction of C1-INH with thrombin in both purified systems and human plasma. For this purpose, we used several methods: (1) sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting analysis; (2) enzyme-linked immunosorbent assays to measure complexes between C1-INH and thrombin and inactivated C1-INH; and (3) kinetic studies using a chromogenic assay. We found that the interaction of purified C1-INH with thrombin is associated with the formation of bimolecular complexes of molecular weight (Mr) 130 000 and 120 000 as well as with the appearance of a cleaved form of C1-INH of Mr 97 000. The kinetic studies of inhibition of thrombin by C1-INH showed an average second-order rate constant of 19/s per mol/l, which was significantly increased in the presence of heparin. The addition of thrombin to human plasma was not associated with detectable C1-INH-thrombin complex formation or with cleavage of C1-INH. In conclusion, our data demonstrate that C1-INH upon interaction with thrombin, in part, forms enzyme-inhibitor complexes and, in part, is cleaved. The low second-order rate constant and the lack of a significant interaction in plasma suggest that the inhibition of thrombin by C1-INH has a minor role in circulating blood; however, its role might be important at the endothelial surface, where high concentrations of glycosaminoglycans occur.

DrugBank Data that Cites this Article

Drugs

Conestat alfa

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Conestat alfa	Prothrombin	Protein	Humans	Yes	Inhibitor	Details
Human C1-esterase inhibitor	Prothrombin	Protein	Humans	Unknown	Inhibitor	Details