Arachidonic acid is metabolized in the vascular endothelium to epoxytrienoic acids (EETs or EpETrEs) by cytochrome P450 enzymes. The EETs are released in response to acetylcholine, bradykinin, arachidonic acid, or cyclic stretch.
1 (±)14(15)-EET-SI is the methyl sulfonamide analog of 14(15)-EET. This substitution results in a metabolically more stable compound because it is not sensitive to β-
oxidation or membrane esterification. (±)14(15)-EET-SI is equipotent to 14(15)-EET in vascular agonist activity as measured by relaxation of precontracted bovine coronary arteries.
1 In addition, 14(15)-EET and the methyl sulfonamide analog both stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells.
2
1. Gauthier, K.M., Falck, J.R., Reddy, L.M., et al. 14,15-EET analogs: Characterization of structural requirements for agonist and antagonist activity in bovine coronary arteries Pharmacol. Res. 49(6),515-524(2004).
2. Chen, J.K., Falck, J.R., Reddy, K.M., et al. Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells J. Biol. Chem. 273(44),29254-29261(1998).
