carboxypeptidase-b and 2-mercaptomethyl-3-guanidinoethylthiopropionic-acid

Procarboxypeptidase B (also known as thrombin-activatable fibrinolysis inhibitor) is a recently described plasma zymogen known to be activated by thrombin in plasma. Carboxy-terminal lysine residues from partially degraded fibrin are important for the binding and activation of plasminogen, and carboxypeptidase B, an active form of procarboxypeptidase B, has been shown to inhibit fibrinolysis by eliminating these residues. The present paper investigates the effects of carboxypeptidase B inhibitors, DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MGPA) and potato-derived carboxypeptidase inhibitor (CPI), on tissue factor (TF)-induced microthrombosis in rats. Intravenous injection of MGPA (3 mg/kg and higher) or CPI (0.3 mg/kg and higher) after microthrombi formation dramatically attenuated TF-induced glomerular fibrin deposition with an increase in plasma levels of D-dimer. These results indicate that carboxypeptidase B inhibitors can enhance endogenous fibrinolysis and reduce thrombi in the TF-induced microthrombosis model after systemic administration even after thrombi formation.

Topics: 3-Mercaptopropionic Acid; Animals; Carboxypeptidase B; Carboxypeptidases; Dose-Response Relationship, Drug; Fibrin; Fibrinolysis; Kidney; Kidney Glomerulus; Male; Protease Inhibitors; Rats; Rats, Wistar; Thromboplastin; Thrombosis

The investigation of inulin-induced conversion of human factor B in serum by isoelectrofocusing revealed physiological modifications in the primary structure of the Ba fragment. Evidence has been obtained that a nascent Ba, generated by the hydrolytic action of the D component on B in serum, was a short-lived product and that a fast release of carboxy-terminal arginine and lysine residues occurred involving a serum carboxypeptidase B enzyme.

Topics: 3-Mercaptopropionic Acid; Aminocaproates; Carboxypeptidase B; Carboxypeptidases; Complement Factor B; Enzyme Precursors; Humans; Inulin; Isoelectric Focusing