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Eicosapentaenoic acid inhibits the release of 14C-prostacyclin from a perfused tissue after incorporation of 14C-prostaglandin precursors

  • H. Juan
  • W. Sametz
Article
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Summary

  1. 1.

    The isolated rabbit ear was labeled by perfusion either with 14C-arachidonic acid (AA) or 14C-dihomo-γ-linolenic acid (DGLA). The influence of unlabeled eicosapentaenoic acid (EPA) on the release and metabolism of the labeled prostaglandin (PG) precursors was studied with the aid of radio-thin-layer-chromatography (TLC).

     
  2. 2.

    After incorporation of 14C-AA, the ionophore A 23187 (10 μg) stimulated the release of products comigrating on TLC plates with authentic PGI2 (measured as 6-keto-PGF1α), PGE2, PGD2 and AA. In unlabeled ears, A 23187 (10 μg) stimulated the release of PGI2 and PGE2 (determined by radioimmunoassay) in similarly relative amounts as found for the labeled products. The release of PGD2 was not measured.

     
  3. 3.

    After incorporation of 14C-DGLA, A 23187 (10 μg) stimulated the release of labeled products comigrating in several TLC-systems with 6-keto-PGF1α (but not PGF1α), PGE1, PGD1 and DGLA.

     
  4. 4.

    After incorporation of 14C-AA, infusion of unlabeled EPA (0.1, 1 and 10 μg/ml) reduced the release of 14C-PGI2 but not of the other bisenoic PGs. Furthermore, in ears labeled with 14C-DGLA, EPA strongly reduced the release of a product comigrating with 6-keto-PGF1α and to a lesser extent of a product comigrating with PGE1.

     
  5. 5.

    Infusion of unlabeled EPA (1 and 10 μg/ml) did not reduce the release of 14C-AA or 14C-DGLA indicating that a phospholipase A2 was probably not inhibited by EPA.

     
  6. 6.

    It is concluded that EPA inhibits PGI2 synthase rather than cyclooxygenase since after incorporation of 14C-AA, only the release of PGI2 is reduced.

     

After incorporation into the tissue, 14C-DGLA appears to be partly desaturated into 14C-AA since 4 h after labeling a product is released comigrating with 6-keto-PGF1α (PGI2). EPA more strongly inhibits the formation of this product than the release of PGI2 from ears after incorporation of 14C-AA. These findings throw some light onto the mechanism by which EPA influences the biosynthesis of PGs but do not, however, explain the antithrombotic effect of EPA.

Key words

Eicosapentaenoic acid 14C-Arachidonic acid 14C-Dihomo-γ-linolenic acid Perfused organ 14C-Prostaglandin release 
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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • H. Juan
    • 1
  • W. Sametz
    • 1
  1. 1.Institut für experimentelle und klinische PharmakologieGrazAustria

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