ArticleThe Journal of biological chemistry2009
Endothelin-1 inhibits thick ascending limb transport via Akt-stimulated nitric oxide production.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 69 citations in OpenAlex.
- Nitric oxide mediates ET-1-induced-inhibition of NPPB-sensitive ClThe Journal of biological chemistry · 2026Article
- G-Protein-Coupled Receptors in Chronic Kidney Disease Induced by Hypertension and Diabetes.Cells · 2025Review
- Sex differences in solute transport along the nephrons: effects of NaAmerican journal of physiology. Renal physiology · 2020Article
- Angiotensin-(1-7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb.Physiological reports · 2019Article
- Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension.Physiological reviews · 2019Review
- Nephron-Specific Disruption of Nitric Oxide Synthase 3 Causes Hypertension and Impaired Salt Excretion.Journal of the American Heart Association · 2018Article
- Role of renal transporters and novel regulatory interactions in the TAL that control blood pressure.Physiological genomics · 2017Review
- Solute transport and oxygen consumption along the nephrons: effects of Na+ transport inhibitors.American journal of physiology. Renal physiology · 2016Article
- Dual inhibition of renin-angiotensin-aldosterone system and endothelin-1 in treatment of chronic kidney disease.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Angiotensin II-mediated hypertension impairs nitric oxide-induced NKCC2 inhibition in thick ascending limbs.American journal of physiology. Renal physiology · 2016Article
- Physiological role of aquaporin 5 in salivary glands.Pflugers Archiv : European journal of physiology · 2016Review
- New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors.World journal of biological chemistry · 2016Review
- Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaCα in Obstructive Kidney Disease.Scientific reports · 2015Article
- Sex differences in proximal and distal nephron function contribute to the mechanism of idiopathic hypercalcuria in calcium stone formers.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Endothelin Blockade in Diabetic Kidney Disease.Journal of clinical medicine · 2015Review
- Endothelin and renal ion and water transport.Seminars in nephrology · 2015Review
- Angiotensin II-induced hypertension blunts thick ascending limb NO production by reducing NO synthase 3 expression and enhancing threonine 495 phosphorylation.American journal of physiology. Renal physiology · 2015Article
- Article
- Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model.BioMed research international · 2015Article
- The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.Infection and immunity · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelin-1 inhibits sodium reabsorption in the thick ascending limb (THAL) via stimulation of nitric oxide (NO) production. The mechanism whereby endothelin-1 stimulates THAL NO is unknown. We hypothesized that endothelin-1 stimulates THAL NO production by activating phosphatidylinositol 3-kinase (PI3K), stimulating Akt activity, and phosphorylating NOS3 at Ser1177. This enhances NO production and inhibits sodium transport. We measured 1) NO production by fluorescence microscopy using DAF2-DA, 2) Akt activity using a fluorescence resonance energy transfer-based Akt reporter, 3) phosphorylated NOS3 and Akt by Western blotting, and 4) NKCC2 activity by fluorescence microscopy. In isolated THAL, endothelin-1 (1 nmol/liter) increased NO production from 0.23 +/- 0.24 to 2.81 +/- 0.32 fluorescence units/min (p < 0.001; n = 5) but failed to stimulate NO production in THALs isolated from NOS3-/- mice. Wortmannin (150 nmol/liter), a PI3K inhibitor, reduced endothelin-1-stimulated NO by 83% (0.49 +/- 0.13 versus 3.31 +/- 0.49 fluorescence units/min for endothelin-1 alone; p < 0.006; n = 5). Endothelin-1 stimulated Akt activity by 0.16 +/- 0.02 arbitrary units as measured by fluorescence resonance energy transfer (p < 0.001; n = 5) and increased phosphorylation of Akt at Ser473 by 56 +/- 11% (p < 0.002; n = 7). Dominant-negative Akt blocked endothelin-1-induced NO by 60 +/- 8% (p < 0.001 versus control; n = 6), and an Akt inhibitor had a similar effect. Endothelin-1 increased phosphorylation of NOS3 at Ser1177 by 89 +/- 24% (p < 0.01; n = 7) but had no effect on Ser633. Endothelin-1 inhibited NKCC2 activity, an effect that was blocked by dominant-negative Akt and NOS inhibition. We conclude that endothelin-1 stimulates THAL NO production by activating PI3K, stimulating Akt activity, and phosphorylating NOS3 at Ser1177. This enhances NO production and inhibits sodium transport.
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