Epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel activity by extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated phosphorylation

Abstract

Background: The epoxygenase metabolites (EETs) inhibit ENaC by unknown mechanisms. Results: 14, 15-EET stimulates an ERK1/2-catalyzed inhibitory phosphorylation of the ENaC β and y subunits. Conclusion: A CYP2C44 epoxygenase/ERK1/2-mediated pathway for ENaC regulation has been characterized. Significance: Roles for human CYP2C8 and CYP2C9 as antihypertensive epoxygenases and for the EETs as antihypertensive drug targets are proposed.© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.