Application of imidazole as a selective inhibitor thromboxane synthetase in human platelets.
AUTOR(ES)
Needleman, P
RESUMO
Human platelet suspensions release a rabbit-aorta-contracting substance (previously identified as thromboxane A2) during aggregation produced by arachidonic acid, prostaglandin endoperoxide, thrombin, and collagen. Incubation of platelets with imidazole did not interfere with the aggregation produced by these agonists but markedly reduced the generation of the rabbit-aorta-contracting substance. We find that imidazole inhibited the conversion of exogenous or endogenous prostaglandin endoperoxide into thromboxane A2-Imidazole selectively inhibits thromboxane synthetase in intact human platelets, because this agent blocks the conversion of [14C]arachidonate into [14C]thromboxane B2 but does not inhibit the conversion of [14C]arachidonate into [14C]prostaglandin E2. The inhibition of thromboxane synthetase by imidazole is not the result of an alteration in platelet 3':5'-cyclic AMP levels. These results illustrate the utility of imidazole as a pharmacological tool and demonstrate the two unique and dissociable properties of the endoperoxides themselves--their ability to aggregate platelets and their enzymatic conversion to the potent vasoconstrictor thromboxane.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=430864Documentos Relacionados
- Regulation of thromboxane receptor activation in human platelets.
- Resolution of prostaglandin endoperoxide synthase and thromboxane synthase of human platelets.
- Solubilization of a thromboxane A2/prostaglandin H2 antagonist binding site from human platelets.
- Distinct platelet thromboxane A2/prostaglandin H2 receptor subtypes. A radioligand binding study of human platelets.
- Detection and partial characterization of an inhibitor of plasminogen activator in human platelets.
