Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activators

Birgit Lauterbach, Eduardo Barbosa-Sicard, Mong Heng Wang, Horst Honeck, Eva Kärgel, Jürgen Theuer, Michal L. Schwartzman, Hermann Haller, Friedrich C. Luft, Maik Gollasch, Wolf Hagen Schunck

Research output: Contribution to journalArticlepeer-review

115 Scopus citations


P450-dependent arachidonic acid (AA) metabolites regulate arterial tone by modulating calcium-activated (BK) potassium channels in vascular smooth muscle cells (VSMC), Because eicosapentaenoic acid (EPA) has been reported to improve vascular function, we tested the hypothesis that P450-dependent epoxygenation of EPA produces alternative vasoactive compounds. We synthesized the 5 regioisomeric epoxyeicosattrienoic acids (EETeTr) and examined them for effects on K+ currents in rat cerebral artery VSMCs with the patch-clamp technique. 11(R),12(S)-epoxyeicosatrienoic acid (50 nmol/L) was used for comparison and stimulated K+ currents 6-fold at +60 mV. However, 17(R),18(S)-EETeTr elicited a more than 14-fold increase, 17(S),18(R)-EET and the remaining four regioisomers were inactive. The effect of 17(R),18(S)-EETeTr was blocked by tetraethylammonium but not by 4-aminopyridine. VSMCs expressed P450s 4A1 and 4A3. Recombinant P450 4A1 hydroxylated EPA at C-19 and C-20 and epoxygenated the 17,18-double bond, yielding the R, S- and S, R-enantiomers in a ratio of 64:36. We conclude that 17(R),18(S)-EETeTr represents a novel, potent activator of BK potassium channels. Furthermore, this metabolite can be directly produced in VSMCs. We suggest that 17(R),18(S)-EETeTr may function as an important hyperpolarizing factor, particularly with EPA-rich diets.

Original languageEnglish (US)
Pages (from-to)609-613
Number of pages5
Issue number2 II
StatePublished - 2002
Externally publishedYes


  • Cytochrome P450
  • Endothelium-derived factors
  • Potassium channels
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Internal Medicine


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