Effects of acetylthrombin on protein C activation and fibrinogen clotting.
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.
Nakagomi
K
K
Bio-organic Chemistry Division, Meiji Institute of Health Science, Meiji Milk Products Co. Ltd., Odawara, Japan.
Ajisaka
K
K
Yokota
I
I
D000577:Amides / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D004151:Dipeptides; D005340:Fibrinogen / Q000187:drug effects* / Q000378:metabolism; D006629:Hirudins / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011486:Protein C / Q000187:drug effects*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000494:pharmacology; D018179:Receptors, Thrombin; D012697:Serine Endopeptidases / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors; D013379:Substrate Specificity; D013917:Thrombin / Q000494:pharmacology*
D000577:Amides; D000991:Antithrombins; D004151:Dipeptides; D006629:Hirudins; D010880:Piperidines; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D015842:Serine Proteinase Inhibitors; D010649:Phenylalanine; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D000990:Antithrombin III; D005340:Fibrinogen; C054648:N-dansyl-(1,4-guanidino)phenylalanine piperdide; D012697:Serine Endopeptidases; C012163:N-acetylthrombin; D013917:Thrombin