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Thromb Haemost 1983; 49(02): 096-101
DOI: 10.1055/s-0038-1657330
Original Article
Schattauer GmbH Stuttgart

Selective Inhibition of Thromboxane Synthetase with Dazoxiben - Basis of Its Inhibitory Effect on Platelet Adhesion

V C Menys
The University Department of Medicine, The General Infirmary, Leeds, England
,
J A Davies
The University Department of Medicine, The General Infirmary, Leeds, England
› Author Affiliations
Further Information

Publication History

Received 09 August 1982

Accepted 25 January 1983

Publication Date:
18 July 2018 (online)

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Summary

Platelet 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.

Keywords

Platelet adhesion - Dazoxiben - Thromboxane A2 - Prostacyclin - Prostaglandin endoperoxides
 

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