Feedback regulation of platelet function by 12S-hydroxyeicosatetraenoic acid: inhibition of arachidonic acid liberation from phospholipids.
We have proposed a mechanism that platelet aggregation is regulated by its 12-lipoxygenase product, 12S-hydroxyeicosatetraenoic acid (12-HETE) (Sekiya, F., Takagi, J. and Saito, Y. (1989) Thrombos. Res. 56, 407-415). Inhibition of endogenous 12-HETE production by 15-HETE, a specific inhibitor of 12-lipoxygenase, accelerated aggregation of bovine platelets in response to collagen and arachidonic acid liberation from phospholipids was enhanced. Exogenously added 12-HETE suppressed collagen-induced liberation of arachidonic acid and the aggregation was also inhibited. On the other hand, 12-HETE did not interfere with thromboxane synthesis from free arachidonic acid in a cell-free system. These observations suggest that 12-HETE exerts a negative feedback to prevent excess aggregation through interference with arachidonic acid liberation from membrane phospholipids.
Sekiya
F
F
Department of Biological Sciences, Tokyo Institute of Technology, Japan.
Takagi
J
J
Sasaki
K
K
Kawajiri
K
K
Kobayashi
Y
Y
Sato
F
F
Saito
Y
Y
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle; D005246:Feedback; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism*; D010974:Platelet Aggregation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D010743:Phospholipids; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases