1. 12S-hydroxyeicosatetraenoic acid plays a central role in the regulation of platelet activation.
- Author
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Sekiya F, Takagi J, Usui T, Kawajiri K, Kobayashi Y, Sato F, and Saito Y
- Subjects
- 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Alprostadil pharmacology, Animals, Cattle, Cyclic AMP blood, Dose-Response Relationship, Drug, Drug Synergism, In Vitro Techniques, Kinetics, Thrombin pharmacology, Hydroxyeicosatetraenoic Acids pharmacology, Platelet Activation, Platelet Aggregation drug effects
- Abstract
When platelets are activated by the recognition of exposed collagen fibers, they start synthesizing two major arachidonic acid metabolites, i.e. thromboxane A2 and 12S-hydroxyeicosatetraenoic acid (12-HETE) via cyclooxygenase and 12-lipoxygenase pathways, respectively. Although the physiological role of the former is well established, that of the latter has not been fully elucidated. Recently, we have revealed that 12-HETE interferes with collagen-induced platelet aggregation [Sekiya, F. et al. (1990) Biochim. Biophys. Acta 1044, 165-168]. In the present paper, we show that this substance enhances thrombin-induced aggregation of bovine platelets, in sharp contrast with the case of collagen. Additionally, 12-HETE is able to prevent the prostaglandin E1-induced elevation of platelet cAMP level and counteracts its inhibitory effect on platelet aggregations. With these observations, we propose a novel self-regulatory mechanism of platelets where 12-HETE plays a key role; it switches sensitivity of platelets from the primary agonist (collagen) to the secondary one (thrombin), and cancels the inhibitory effect of cAMP elevators.
- Published
- 1991
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