Biological activity and metabolism of 20-hydroxyeicosatetraenoic acid in the human platelet

Br J Pharmacol. 1992 Jun;106(2):267-74. doi: 10.1111/j.1476-5381.1992.tb14327.x.


1. The cytochrome P-450 metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), was found to be a potent, dose-dependent inhibitor of platelet aggregation and inhibitor of thromboxane biosynthesis induced by arachidonic acid (IC50 5.2 +/- 1.5 microM), A23187 (IC50 16.2 +/- 5.4 microM), and U46619 (IC50 7.8 +/- 2.4 microM). 20-HETE did not inhibit thrombin-induced aggregation. 2. The human platelet metabolized 20-HETE to a series of novel metabolites formed by cyclo-oxygenase as well as lipoxygenase pathways. The structures of the metabolites were identified by mass spectrometry as 20-hydroxy-thromboxane B2, 12,17-dihydroxyheptadecatrienoic acid, 12,20-dihydroxyeicosatetraenoic acid, and 11,20-dihydroxyeicosatetraenoic acid. 3. The identification of the 11-hydroxy metabolite of 20-HETE suggests that 20-HETE is less efficiently cyclized to an endoperoxide intermediate by cyclo-oxygenase than is arachidonate. 4. Although some biological activity of 20-HETE may be related to competition with endogenous arachidonate for cyclo-oxygenase metabolism, the predominant mechanism of action of 20-HETE appears to be through antagonism of the prostaglandin H2/thromboxane A2 receptor.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Arachidonate 12-Lipoxygenase / metabolism
  • Blood Platelets / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyclic AMP / metabolism
  • Fatty Acids, Unsaturated
  • Humans
  • Hydrazines / pharmacology
  • Hydroxyeicosatetraenoic Acids / blood
  • Hydroxyeicosatetraenoic Acids / physiology*
  • In Vitro Techniques
  • Platelet Activation / physiology
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / metabolism
  • Prostaglandin H2
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandins H / metabolism
  • Thromboxane A2 / antagonists & inhibitors
  • Thromboxane A2 / biosynthesis


  • Bridged Bicyclo Compounds, Heterocyclic
  • Fatty Acids, Unsaturated
  • Hydrazines
  • Hydroxyeicosatetraenoic Acids
  • Platelet Aggregation Inhibitors
  • Prostaglandins H
  • Prostaglandin H2
  • Thromboxane A2
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • SQ 29548
  • Cyclic AMP
  • Arachidonate 12-Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases