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.
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Authors | K Nakagomi, K Ajisaka, I Yokota |
Journal | Thrombosis research
(Thromb Res)
Vol. 59
Issue 4
Pg. 713-22
(Aug 15 1990)
ISSN: 0049-3848 [Print] United States |
PMID | 1964250
(Publication Type: Journal Article)
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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
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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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