17R(18S)-EpETE (Synonyms: 17R,18S-EEQ, 17R,18S-epoxy Eicosatetraenoic Acid)

17R(18S)-EpETE is an oxylipin and a cytochrome P450 metabolite of eicosapentaenoic acid .^1,2 17R(18S)-EpETE is an activator of large-conductance calcium-activated potassium (BK_Ca) channels, increasing the potassium current amplitude by 15-fold in isolated rat cerebral artery vascular smooth muscle cells (VSMCs) at +60 mV when used at a concentration of 50 nM.² It has negative chronotropic effects in isolated neonatal rat cardiomyocytes (NRCMs; EC₅₀ = ~1-2 nM) and prevents calcium-induced increases in the spontaneous beating of NRCMs.^3,4

1.Schwarz, D., Kisselev, P., Ericksen, S.S., et al.Arachidonic and eicosapentaenoic acid metabolism by human CYP1A1: Highly steroselective formation of 17(R), 18(S)-epoxyeicosatetraenoic acidBiochem. Pharmacol.67(8)1445-1457(2004) 2.Lauterbach, B., Barbosa-Sicard, E., Wang, M.H., et al.Cytochrome P450-dependent eicosapentaenoic acid metabolites are novel BK channel activatorsHypertension39(2 Pt. 2)609-613(2002) 3.Falck, J.R., Wallukat, G., Puli, N., et al.17(R),18(S)-Epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analoguesJ. Med. Chem.54(12)4109-4118(2011) 4.Arnold, C., Markovic, M., Blossey, K., et al.Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of omega-3 fatty acidsJ. Biol. Chem.285(43)32720-32733(2010)