Occurrence of the 15-hydroxy derivative of dihomogammalinolenic acid in human platelets and its biological effect

Biochim Biophys Acta. 1988 Sep 2;962(1):149-54. doi: 10.1016/0005-2760(88)90106-3.

Abstract

Various polyunsaturated fatty acids are oxygenated by platelet lipoxygenase at the n - 9 position. The present paper reports that platelets may also oxygenate dihomogammalinolenic acid (20:3(n - 6)) at the n - 6 position, leading to the formation of substantial amounts of 15-OH-8,11,13-20:3 characterized by its ultraviolet spectrum, HPLC and GC-MS analysis. Its formation was inhibited by aspirin and eicosatetraynoic acid, but not by heneicosatetraynoic acid, a specific inhibitor of platelet lipoxygenase. The time-course of its synthesis was very close to that of 12-OH-8,10-17:2 (HHD), the non-cyclic cyclooxygenase side-product, but different from that of 12-OH-8,10,14-20:3, the platelet lipoxygenase end-product of 20:3 (n - 6). Overall, these results indicate that 15-OH-20:3 could be a cyclooxygenase metabolite generated in an aborted process. Like other monohydroxy derivatives of polyenoic fatty acids, 15-OH-20:3 was able to modulate thromboxane-induced platelet aggregation. The derivative exhibited a biphasic effect on the aggregation. It potentiated at concentrations below 2.10(-7) M and inhibited at higher doses. It is concluded that the potentiating activity might explain at least part of the transient enhancement of the platelet activation observed in adding exogenous 20:3(n - 6).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • 8,11,14-Eicosatrienoic Acid / analogs & derivatives
  • 8,11,14-Eicosatrienoic Acid / blood*
  • Aspirin / pharmacology
  • Blood Platelets / analysis*
  • Blood Platelets / metabolism
  • Blood Platelets / physiology
  • Drug Synergism
  • Fatty Acids, Unsaturated / blood*
  • Humans
  • Hydroxylation
  • Kinetics
  • Leukotriene B4
  • Linolenic Acids / blood*
  • Linolenic Acids / physiology
  • Platelet Aggregation / drug effects
  • Prostaglandin Endoperoxides, Synthetic

Substances

  • Fatty Acids, Unsaturated
  • Linolenic Acids
  • Prostaglandin Endoperoxides, Synthetic
  • 15-hydroxy-8,11,13-eicosatrienoic acid
  • Leukotriene B4
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • 8,11,14-Eicosatrienoic Acid
  • Aspirin