Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion
| Autor: | J A Davies, V C Menys |
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| Rok vydání: | 1983 |
| Předmět: | |
| Zdroj: | Thrombosis and Haemostasis. 49:096-101 |
| ISSN: | 2567-689X 0340-6245 |
| DOI: | 10.1055/s-0038-1657330 |
| Popis: | SummaryPlatelet adhesion to rabbit aortic subendothelium or collagen-coated glass was quantitated in a rotating probe device by uptake of radio-labelled platelets. Under conditions in which aspirin had no effect, dazoxiben, a selective inhibitor of thromboxane synthetase, reduced platelet adhesion to aortic subendothelium by about 40% but did not affect adhesion to collagen-coated glass. Pre-treatment of aortic segments with 15-HPETE, a selective inhibitor of PGI2-synthetase, abolished the inhibitory effect of dazoxiben on adhesion. Concentrations of 6-oxo-PGFlα in the perfusate were raised in the presence of dazoxiben alone, and following addition of thrombin (10 units/ml) there was a 2-3 fold increase in concentration. Perfusion of damaged aorta with platelets labelled with (14C)-arachidonic acid in the presence of thrombin and dazoxiben resulted in the appearance of (14C)-labelled-6-oxo-PGFiα. Inhibition of thromboxane synthetase limits platelet adhesion probably by promoting vascular synthesis of PGI2 from endoperoxides liberated from adherent platelets, which subsequently promotes detachment of cells from the surface. |
| Databáze: | OpenAIRE |
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