12-HETE inhibits the binding of PGH2/TXA2 receptor ligands in human platelets

Thromb Res. 1991 Jul 15;63(2):239-48. doi: 10.1016/0049-3848(91)90287-7.

Abstract

12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), the end-lipoxygenase product of arachidonic acid in platelets has been previously shown to prevent PGH2/TxA2-induced aggregation. From the present study, we show that 12-HETE inhibits the binding of [125I]-PTA-OH, a thromboxane antagonist, to platelet membranes with an IC50 of 8 microM. This value is in accordance with previously reported 12-HETE concentrations required to prevent the aggregation induced by TxA2 mimetics, the methano analogues of PGH2, U44069 and U46619. When [3H]-U44069 was used as a thromboxane agonist to label intact platelets, 12-HETE also inhibited its binding. We conclude that part of the inhibitory effect of 12-HETE on PGH2/TxA2-induced aggregation might be the result of interacting with PGH2/TxA2 receptor sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Depression, Chemical
  • Humans
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Inositol Phosphates / biosynthesis
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Prostaglandin Endoperoxides, Synthetic / antagonists & inhibitors
  • Prostaglandin Endoperoxides, Synthetic / metabolism*
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Prostaglandin H2
  • Prostaglandins H / antagonists & inhibitors
  • Prostaglandins H / metabolism*
  • Receptors, Prostaglandin / drug effects*
  • Receptors, Prostaglandin / metabolism
  • Receptors, Thromboxane
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / antagonists & inhibitors
  • Thromboxane A2 / metabolism*
  • Thromboxane A2 / pharmacology

Substances

  • Hydroxyeicosatetraenoic Acids
  • Inositol Phosphates
  • Platelet Aggregation Inhibitors
  • Prostaglandin Endoperoxides, Synthetic
  • Prostaglandins H
  • Receptors, Prostaglandin
  • Receptors, Thromboxane
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Prostaglandin H2
  • U 44069
  • Thromboxane A2
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • I-PTA-OH