Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new method has been developed to investigate the direct effect of endothelial cells on platelet aggregation in the presence of cultured confluent human EC monolayers. The inside of the disk shaped cuvettes are covered by human umbilical vein ECs. The cuvettes rotate in the light beam of a photometer. In these cuvettes the effect of different aggregation inducers was inhibited in a concentration-dependent manner, e. g. for collagen at 0.5 microgram/ml, ADP at 5 x 10(-7) M, epinephrine at 5 x 10(-7) M and thrombin at 0.05 U/ml final concentration. (Platelet count 5 x 10(5)/microliters). Higher concentrations of the inducers led to irreversible platelet aggregation and were used for testing of antiplatelet drugs. In this system we detected a synergism between the antiaggregatory effect of the EC monolayer and that of SIN 1 (Cassella, Frankfurt/Main) the main metabolite of Molsidomine. 10 micrograms/ml PRP of SIN 1 alone partially inhibited platelet aggregation induced by 1 microgram/ml collagen and 10(-6) M ADP respectively in uncovered aggregation cuvettes. In the presence of an EC monolayer complete inhibition of platelet aggregation was obtained at a 5-fold final concentration of both inducers. After pretreatment of ECs with 1 mmol ASA over 30 min. the antiaggregatory effect of SIN 1 decreased, but was more pronounced (50%) than in uncovered cuvettes (25%).
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PMID:[Effect of SIN 1 on the interactions of endothelial cells and thrombocytes]. 177 29

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin to be aggregated. Unlike molsidomine, SIN-1 when infused (10 and 20 micrograms/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with aspirin (50 mg/kg i.v.). It is suggested that SIN-1 may promote formation of a PGI2-like substance. In humans shortening of euglobulin clot lysis time was observed 60 min after a single ingestion of 2 mg of molsidomine. This fibrinolytic effect of molsidomine was not abolished by the pretreatment of patients with aspirin. Neither molsidomine nor SIN-1 activated fibrinolysis in preformed euglobulin clots in vitro.
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PMID:The influence of molsidomine and its active metabolite SIN-1 on fibrinolysis and platelet aggregation. 391 80

We studied the action of the biologically active metabolite of molsidomine, N-morpholino-N-nitrosoamino-acetonitrile (SIN), on eicosanoid formation and functional behavior of bovine coronary arteries and human platelets in vitro. Glyceryltrinitrate (GTN) and prostaglandin (PG) I2 were used as reference compounds. SIN dose-dependently inhibited the thrombin-, collagen-, and primary ADP-induced platelet aggregation. The IC50 was in the range of 0.1-0.8 mumol/L. At these concentrations SIN also inhibited thromboxane formation, but did not influence the PGI2 biosynthesis of coronary vessels. Molsidomine itself was inactive. GTN stimulated vascular PGI2 formation, but did not modify the platelet aggregation at comparable concentrations. A particularly interesting finding was the dose-dependent and apparently complete inhibition of formation of the hydroperoxide of 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) in human platelets by SIN. The IC50 amounted to 1.7 +/- 0.4 mumol/L and was in the same range as with 5,8,11,14-eicosatetraynoic acid (2.0 +/- 0.3 mumol/L). Although the results may not suggest a common mechanism of the antiaggregatory action of GTN and SIN, they provide no evidence of a similar or dissimilar mechanism of action in vascular smooth muscle.
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PMID:The effects of molsidomine and its metabolite SIN-1 on coronary vessel tone, platelet aggregation, and eicosanoid formation in vitro--inhibition of 12-HPETE biosynthesis. 619 92