ArticleAmerican journal of physiology. Renal physiology2011
Effects of cytochrome P-450 metabolites of arachidonic acid on the epithelial sodium channel (ENaC).
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- Regulation of P450-derived epoxy fatty acids in cardiovascular diseases.Redox biochemistry and chemistry · 2025Article
- The involvement of soluble epoxide hydrolase in the development of cardiovascular diseases through epoxyeicosatrienoic acids.Frontiers in pharmacology · 2024Review
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- Interleukin 6 mediated activation of the mineralocorticoid receptor in the aldosterone-sensitive distal nephron.American journal of physiology. Cell physiology · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Prostaglandin E2 stimulates the epithelial sodium channel (ENaC) in cultured mouse cortical collecting duct cells in an autocrine manner.The Journal of general physiology · 2020Article
- Epoxy Fatty Acids: From Salt Regulation to Kidney and Cardiovascular Therapeutics: 2019 Lewis K. Dahl Memorial Lecture.Hypertension (Dallas, Tex. : 1979) · 2020Article
- Epoxyeicosatrienoic acid metabolites inhibit Kir4.1/Kir5.1 in the distal convoluted tubule.American journal of physiology. Renal physiology · 2020Article
- Soluble Epoxide Hydrolase Inhibition Prevents Experimental Type 4 Cardiorenal Syndrome.Frontiers in molecular biosciences · 2020Article
- Multi-Target Approaches in Metabolic Syndrome.Frontiers in pharmacology · 2020Review
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- A novel dual PPAR-γ agonist/sEH inhibitor treats diabetic complications in a rat model of type 2 diabetes.Diabetologia · 2018Article
- Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the pathogenesis of renal dysfunction in cirrhosis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018Article
- 20-HETE: Hypertension and Beyond.Hypertension (Dallas, Tex. : 1979) · 2018Review
- Review
- Epoxygenase Inhibitors Attenuate the Stimulatory Effect of Glutoxim on NaDoklady. Biochemistry and biophysics · 2018Article
- Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects.Hypertension (Dallas, Tex. : 1979) · 2018Article
- Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017Review
- The Lectin-like Domain of TNF Increases ENaC Open Probability through a Novel Site at the Interface between the Second Transmembrane and C-terminal Domains of the α-Subunit.The Journal of biological chemistry · 2016Article
- Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism.Biochimica et biophysica acta · 2015Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Sodium reabsorption via the epithelial Na(+) channel (ENaC) in the aldosterone-sensitive distal nephron plays a central role in the regulation of body fluid volume. Previous studies have indicated that arachidonic acid (AA) and its metabolite 11,12-EET but not other regioisomers of EETs inhibit ENaC activity in the collecting duct. The goal of this study was to investigate the endogenous metabolism of AA in cultured mpkCCD(c14) principal cells and the effects of these metabolites on ENaC activity. Liquid chromatography/mass spectrometry analysis of the mpkCCD(c14) cells indicated that these cells produce prostaglandins, 8,9-EET, 11,12-EET, 14,15-EET, 5-HETE, 12/8-HETE, and 15-HETE, but not 20-HETE. Single-channel patch-clamp experiments revealed that 8,9-EET, 14,15-EET, and 11,12-EET all decrease ENaC activity. Neither 5-, 12-, nor 15-HETE had any effect on ENaC activity. Diclofenac and ibuprofen, inhibitors of cyclooxygenase, decreased transepithelial Na(+) transport in the mpkCCD(c14) cells. Inhibition of cytochrome P-450 (CYP450) with MS-PPOH activated ENaC-mediated sodium transport when cells were pretreated with AA and diclofenac. Coexpression of CYP2C8, but not CYP4A10, with ENaC in Chinese hamster ovary cells significantly decreased ENaC activity in whole-cell experiments, whereas 11,12-EET mimicked this effect. Thus both endogenously formed EETs and their exogenous application decrease ENaC activity. Downregulation of ENaC activity by overexpression of CYP2C8 was PKA dependent and was prevented by myristoylated PKI treatment. Biotinylation experiments and single-channel analysis revealed that long-term treatment with 11,12-EET and overexpression of CYP2C8 decreased the number of channels in the membrane. In contrast, the acute inhibitory effects are mediated by a decrease in the open probability of the ENaC. We conclude that 11,12-EET, 8,9-EET, and 14,15-EET are endogenously formed eicosanoids that modulate ENaC activity in the collecting duct.
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