11R(12S)-EET

11R(12S)-EET is an oxylipin and a metabolite of arachidonic acid .^[1],[2] It is selectively formed from arachidonic acid by the cytochrome P450 (CYP) isoform CYP2C23 and CYP2C24 over CYP2B2, as well as CYP2C8 over CYP2C9. 11R(12S)-EET (50 nM) activates large-conductance calcium-activated potassium channels (K_Ca1.1/BK) in isolated rat coronary small arterial smooth muscle cells and binds to isolated guinea pig monocytes in a competitive binding assay using [^[3]H]14(15)-EET (K_i = 595.1 nM).^3,4 It inhibits the epithelial sodium channel (ENaC) in a patch-clamp assay using isolated rat cortical collecting duct tubules when used at a concentration of 100 nM.^[5] 11R(12S)-EET induces dilation of precontracted isolated canine epicardial arterioles (EC₅₀ = 6.3 pM) and denuded porcine subepicardial arterioles (EC₅₀ = 1.6 pM).^[3] It induces migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 5 µM.^[6]

References:
[1].Capdevila, J.H., Falck, J.R., and Harris, R.C.Cytochrome P450 and arachidonic acid bioactivation: Molecular and functional properties of the arachidonate monooxygenaseJ. Lipid Res.41(2)163-181(2000).
[2].Daikh, B.E., Lasker, J.M., Raucy, J.L., et al.Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C91J. Pharmacol. Exp. Ther.271(3)1427-1433(1994).
[3].Zhang, Y., Oltman, C.L., Lu, T., et al.EET homologs potently dilate coronary microvessels and activate BKCa channelsAm. J. Physiol. Heart Circ. Physiol.280(6)H2430-H2440(2001).
[4].Wong, P.Y.-K., Lai, P.-S., and Falck, J.R.Mechanism and signal transduction of 14 (R), 15 (S)-epoxyeicosatrienoic acid (14,15-EET) binding in guinea pig monocytesProstaglandins Other Lipid Mediat.62(4)321-333(2000).
[5].Sun, P., Lin, D.H., Yue, P., et al.High potassium intake enhances the inhibitory effect of 11,12-EET on ENaCJ. Am. Soc. Nephrol.21(10)1667-1677(2010).
[6].Ding, Y., Frömel, T., Popp, R., et al.The biological actions of 11,12-epoxyeicosatrienoic acid in endothelial cells are specific to the R/S-enantiomer and require the Gs proteinJ. Pharmacol. Exp. Ther.350(1)14-21(2014).