title: 12S-hydroxyeicosatetraenoic acid plays a central role in the regulation of platelet activation.
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.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Sekiya
authors.forename: J
authors.initials: J
authors.lastname: Takagi
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: K
authors.initials: K
authors.lastname: Kawajiri
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000242:Cyclic AMP; D013917:Thrombin; D000527:Alprostadil