The Effect of Some Synthetic Arginyl and Lysyl Compounds on Clotting and Fibrinolysis

1972 ◽  
Vol 28 (02) ◽  
pp. 289-298 ◽  
Author(s):  
M. J Weinstein ◽  
R. F Doolittle
Keyword(s):  
Methyl Ester ◽  
Thrombin Activation

SummaryThe effects of a number of synthetic arginyl- and lysyl-compounds on clotting and fibrinolysis have been studied. The lysyl derivatives had no significant effect on the clotting of recalcified plasma or recalcified euglobulin preparations, but tosyllysine (TL) and tosyllysine methyl ester (TLME) were very effective inhibitors of fibrinolysis. Certain arginyl-peptides (in particular, tosylarginylsarcosine methyl ester) were very effective at delaying clotting in these systems. These same substances gave rise to an exaggerated thrombin production, however, evidently by interfering with the natural thrombin activation of plasma antithrombin(s).

The Activity of Plasma, Serum, Thrombin, and Plasmin toward Synthetic Trypsin Substrates

1968 ◽  
Vol 19 (01/02) ◽  
pp. 099-106 ◽  
Author(s):  
E Szczeklik ◽  
M Orłowski ◽  
A Szczeklik ◽  
Barbara Narczewska
Keyword(s):  
Methyl Ester ◽  
Proteolytic Activity ◽  
Trypsin Activity ◽  
Plasmin Activity ◽  
Thrombin Activity ◽  
Rate Of Reaction ◽  
Thrombin Activation

SummaryP-toluenesulphonyl-1-arginine methyl ester and two amide substrates of arginine (Nα-benzoyl-dl-arginine-p-nitroanilide and Nα-benzoyl-dl-arginine-2-naphthylamide) were employed for studies of the nature of the “trypsin-like” activity in plasma, serum and euglobulins. No data were obtained which might suggest the presence of trypsin activity in either plasma or serum. The evidence indicates that activity toward both amide substrates in plasma and euglobulins is dependent on the generation of thrombin. Activation of plasminogen in euglobulins by streptokinase generated a proteolytic activity toward Nα-benzoyl-dl-arginine-p-nitroanilide but not toward Nα-benzoyl-dl-arginine-2-naphthylamide. The generation and inactivation of thrombin activity in whole plasma may be conveniently followed by using Nα-benzoyl-dl-arginine-p-nitroanilide as substrate.Purified preparations of thrombin and plasmin were shown to split several synthetic amide substrates of arginine. Significant differences between thrombin and plasmin were found in the rate of reaction with these substrates. Of the amide substrates, Nα-carbobenzoxydiglycyl-l-arginine-2-naphthylamide was split most rapidly by both enzymes. This substrate may be conveniently used for the determination of thrombin and plasmin activity.

Thrombin Augments Vascular Cell-dependent Migration of Human Mast Cells: Role of MGF

1997 ◽  
Vol 77 (03) ◽  
pp. 577-584 ◽  
Author(s):  
Mehrdad Baghestanian ◽  
Roland Hofbauer ◽  
Hans G Kress ◽  
Johann Wojta ◽  
Astrid Fabry ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mast Cells ◽  
Umbilical Vein ◽  
Vascular Cells ◽  
Migratory Response ◽  
Thrombin Activation ◽  
Umbilical Vein Endothelial Cells ◽  
Primary Tissue ◽  
Local Expression

SummaryRecent data suggest that auricular thrombosis is associated with accumulation of mast cells (MC) in the upper endocardium (where usually no MC reside) and local expression of MGF (mast cell growth factor) (25). In this study, the role of vascular cells, thrombin-activation and MGF, in MC-migration was analyzed. For this purpose, cultured human auricular endocardial cells (HAUEC), umbilical vein endothelial cells (HUVEC) and uterine-(HUTMEC) and skin-derived (HSMEC) microvascular endothelial cells were exposed to thrombin or control medium, and the migration of primary tissue MC (lung, n = 6) and HMC-1 cells (human MC-line) against vascular cells (supernatants) measured. Supernatants (24 h) of unstimulated vascular cells (monolayers of endocardium or endothelium) as well as recombinant (rh) MGF induced a significant migratory response in HMC-1 (control: 3025 ± 344 cells [100 ± 11.4%] vs. MGF, 100 ng/ml: 8806 ± 1019 [291 ± 34%] vs. HAUEC: 9703 ± 1506 [320.8 ± 49.8%] vs. HUTMEC: 8950 ± 1857 [295.9 ± 61.4%] vs. HSMEC: 9965 ± 2018 [329.4 ± 66.7%] vs. HUVEC: 9487 ± 1402 [313.6 ± 46.4%], p <0.05) as well as in primary lung MC. Thrombin-activation (5 U/ml, 12 h) of vascular cells led to an augmentation of the directed migration of MC as well as to a hirudin-sensitive increase in MGF synthesis and release. Moreover, a blocking anti-MGF antibody was found to inhibit MC-migration induced by unstimulated or thrombin-activated vascular cells. Together, these data show that endocardial and other vascular cells can induce migration of human MC. This MC-chemotactic signal of the vasculature is associated with expression and release of MGF, augmentable by thrombin, and may play a role in the pathophysiology of (auricular) thrombosis.

Activity of Plasmin and Streptokinase-Activator on Substituted Arginine and Lysine Esters

1966 ◽  
Vol 16 (01/02) ◽  
pp. 018-031 ◽  
Author(s):  
S Sherry ◽  
Norma Alkjaersig ◽  
A. P Fletcher
Keyword(s):  
Molecular Structure ◽  
Methyl Ester ◽  
Comparative Studies ◽  
Esterase Activity ◽  
Methyl Esters ◽  
Hydrolytic Activity ◽  
The Other ◽  
Other Hand

SummaryComparative studies have been made of the esterase activity of plasmin and the streptokinase-activator of plasminogen on a variety of substituted arginine and lysine esters. Human plasmin preparations derived by different methods of activation (spontaneous in glycerol, trypsin, streptokinase (SK) and urokinase) are similar in their esterase activity; this suggests that the molecular structure required for such esterase activity is similar for all of these human plasmins. Bovine plasmin, on the other hand, differs from human plasmin in its activity on several of the substrates studied (e.g., the methyl esters of benzoyl arginine and tosyl, acetyl and carbobenzoxy lysine), a finding which supports the view that molecular differences exist between the two animal plasmins. The streptokinase-activator hydrolyzes both arginine and lysine esters but the ratios of hydrolytic activity are distinct from those of plasmin and of other activators of plasminogen. The use of benzoyl arginine methyl ester as a substrate for the measurement of the esterase activity of the streptokinase-activator is described.

Functional Involvement of Thrombospondin in Platelet Aggregation Induced by Low Versus High Concentrations of Thrombin

1986 ◽  
Vol 55 (01) ◽  
pp. 136-142 ◽  
Author(s):  
K J Kao ◽  
David M Shaut ◽  
Paul A Klein
Keyword(s):  
Platelet Aggregation ◽  
Binding Sites ◽  
Inhibitory Effect ◽  
Activated Platelets ◽  
Low Concentrations ◽  
Platelet Binding ◽  
Functional Involvement ◽  
Thrombin Activation ◽  
Platelet Aggregates ◽  
High Concentrations

SummaryThrombospondin (TSP) is a major platelet secretory glycoprotein. Earlier studies of various investigators demonstrated that TSP is the endogenous platelet lectin and is responsible for the hemagglutinating activity expressed on formaldehyde-fixed thrombin-treated platelets. The direct effect of highly purified TSP on thrombin-induced platelet aggregation was studied. It was observed that aggregation of gel-filtered platelets induced by low concentrations of thrombin (≤0.05 U/ml) was progressively inhibited by increasing concentrations of exogenous TSP (≥60 μg/ml). However, inhibition of platelet aggregation by TSP was not observed when higher than 0.1 U/ml thrombin was used to activate platelets. To exclude the possibility that TSP inhibits platelet aggregation by affecting thrombin activation of platelets, three different approaches were utilized. First, by using a chromogenic substrate assay it was shown that TSP does not inhibit the proteolytic activity of thrombin. Second, thromboxane B2 synthesis by thrombin-stimulated platelets was not affected by exogenous TSP. Finally, electron microscopy of thrombin-induced platelet aggregates showed that platelets were activated by thrombin regardless of the presence or absence of exogenous TSP. The results indicate that high concentrations of exogenous TSP (≥60 μg/ml) directly interfere with interplatelet recognition among thrombin-activated platelets. This inhibitory effect of TSP can be neutralized by anti-TSP Fab. In addition, anti-TSP Fab directly inhibits platelet aggregation induced by a low (0.02 U/ml) but not by a high (0.1 U/ml) concentration of thrombin. In conclusion, our findings demonstrate that TSP is functionally important for platelet aggregation induced by low (≤0.05 U/ml) but not high (≥0.1 U/ml) concentrations of thrombin. High concentrations of exogenous TSP may univalently saturate all its platelet binding sites consequently interfering with TSP-crosslinking of thrombin-activated platelets.

Photoinduced N-Demethylation of Rufloxacin and its Methyl Ester Under Aerobic Conditions¶

2002 ◽  
Vol 76 (3) ◽  
pp. 252 ◽  
Author(s):  
Alessandra Belvedere ◽  
Francisco Boscá ◽  
M. Consuelo Cuquerella ◽  
Guido de Guidi ◽  
Miguel A. Miranda
Keyword(s):  
Methyl Ester ◽  
Aerobic Conditions
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