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Effects of acetylthrombin on protein C activation and fibrinogen clotting.

Abstract
Thrombin was acetylated by treatment with acetic anhydride, and the potency for protein C activation and the fibrinogen clotting activity of the resultant acetylthrombin were investigated in vitro and in vivo. The acetylthrombin retained an amidolytic activity to the synthetic substrate, S-2238, and reduced both of the potency for protein C activation and the clotting activity. The potency for protein C activation (0.47% of that of thrombin) was retained more than the clotting activity (0.015% of that of thrombin). The enzymatic activities of acetylthrombin were in inverse proportion to the molecular weights of the substrates, S-2238, protein C, and fibrinogen. Similarly, the inhibitory activity on acetylthrombin was dependent on the molecular weights of the inhibitors, Thromstop, I-2581, hirudin, and antithrombin-III. When acetylthrombin (5000 units/kg body weight) was infused into rabbits, the activated partial thromboplastin time was prolonged to the same extent as that following infusion of thrombin (125 units/kg), but the fibrinogen level was not decreased in contrast to the large decrease following infusion of thrombin. It is suggested that acetylthrombin activates protein C without clotting fibrinogen in vivo.
AuthorsK Nakagomi, K Ajisaka, I Yokota
JournalThrombosis research (Thromb Res) Vol. 59 Issue 4 Pg. 713-22 (Aug 15 1990) ISSN: 0049-3848 [Print] United States
PMID1964250 (Publication Type: Journal Article)
Chemical References
  • Amides
  • Antithrombins
  • Dipeptides
  • Hirudins
  • Piperidines
  • Protein C
  • Receptors, Cell Surface
  • Receptors, Thrombin
  • Serine Proteinase Inhibitors
  • Phenylalanine
  • N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide
  • Antithrombin III
  • Fibrinogen
  • N-dansyl-(1,4-guanidino)phenylalanine piperdide
  • Serine Endopeptidases
  • N-acetylthrombin
  • Thrombin
Topics
  • Amides (metabolism)
  • Amino Acid Sequence
  • Animals
  • Antithrombin III (pharmacology)
  • Antithrombins (pharmacology)
  • Blood Coagulation (drug effects)
  • Dipeptides
  • Fibrinogen (drug effects, metabolism)
  • Hirudins (pharmacology)
  • Male
  • Molecular Sequence Data
  • Partial Thromboplastin Time
  • Phenylalanine (analogs & derivatives, pharmacology)
  • Piperidines (pharmacology)
  • Protein C (drug effects)
  • Rabbits
  • Receptors, Cell Surface (pharmacology)
  • Receptors, Thrombin
  • Serine Endopeptidases (pharmacology)
  • Serine Proteinase Inhibitors
  • Substrate Specificity
  • Thrombin (pharmacology)

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