ArticleAmerican journal of physiology. Renal physiology2010
Ouabain stimulates Na-K-ATPase through a sodium/hydrogen exchanger-1 (NHE-1)-dependent mechanism in human kidney proximal tubule cells.
Article in American journal of physiology. Renal physiology, 2010. 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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36 citing papers in PubMed, 67 citations in OpenAlex.
- Model of ocular surface ion and water transport predicts efficacy of dry eye therapeutics.The Journal of general physiology · 2026Article
- Role of NHERF1 in MicroRNA Landscape Changes in Aging Mouse Kidneys.Biomolecules · 2024Article
- Chronic Ouabain Targets Pore-Forming Claudin-2 and Ameliorates Radiation-Induced Damage to the Rat Intestinal Tissue Barrier.International journal of molecular sciences · 2023Article
- NaBiomedicines · 2023Review
- Bioactive C21 Steroidal Glycosides fromMolecules (Basel, Switzerland) · 2023Article
- Effects of renal denervation on endogenous ouabain in spontaneously hypertensive rats.Acta cirurgica brasileira · 2023Article
- Stress-induced reduction of NaScience advances · 2022Article
- Short-Term Mild Hypoxia Modulates Na,K-ATPase to Maintain Membrane Electrogenesis in Rat Skeletal Muscle.International journal of molecular sciences · 2022Article
- Chronic Ouabain Prevents Radiation-Induced Reduction in the α2 Na,K-ATPase Function in the Rat Diaphragm Muscle.International journal of molecular sciences · 2022Article
- Alleviation of liver cirrhosis and associated portal-hypertension by Astragalus species in relation to their UPLC-MS/MS metabolic profiles: a mechanistic study.Scientific reports · 2022Article
- Ocean Acidification Alters Developmental Timing and Gene Expression of Ion Transport Proteins During Larval Development in Resilient and Susceptible Lineages of the Pacific Oyster (Crassostrea gigas).Marine biotechnology (New York, N.Y.) · 2022Article
- Endogenous Cardiac Steroids in Bipolar Disorder: State of the Art.International journal of molecular sciences · 2022Review
- Phosphorylation of NaThe Journal of membrane biology · 2021Article
- Na,K-ATPase as a target for endogenous cardiotonic steroids: What's the evidence?Genes & diseases · 2021Review
- Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle.International journal of molecular sciences · 2021Article
- Role of endogenous ouabain in the etiology of bipolar disorder.International journal of bipolar disorders · 2021Review
- Circulating Ouabain Modulates Expression of Claudins in Rat Intestine and Cerebral Blood Vessels.International journal of molecular sciences · 2020Article
- Skeletal Muscle Na,K-ATPase as a Target for Circulating Ouabain.International journal of molecular sciences · 2020Article
- Sodium-hydrogen exchanger regulatory factor-1 (NHERF1) confers salt sensitivity in both male and female models of hypertension in aging.Life sciences · 2020Article
- Review
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9 authors at 3 institutions in 1 country.
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Abstract
Recent investigations demonstrate increased Na/H exchanger-1 (NHE-1) activity and plasma levels of ouabain-like factor in spontaneously hypertensive rats. At nanomolar concentrations, ouabain increases Na-K-ATPase activity, induces cell proliferation, and activates complex signaling cascades. We hypothesize that the activity of NHE-1 and Na-K-ATPase are interdependent. To test whether treatment with picomolar ouabain regulates Na-K-ATPase through an NHE-1-dependent mechanism, we examined the role of NHE-1 in ouabain-mediated stimulation of Na-K-ATPase in kidney proximal tubule cell lines [opossum kidney (OK), HK-2, HKC-5, and HKC-11] and rat kidney basolateral membranes. Ouabain stimulated Na-K-ATPase activity and tyrosine phosphorylation in cells that express NHE-1 (OK, HKC-5, and HKC-11) but not in HK-2 cells that express very low levels of NHE-1. Inhibition of NHE-1 with 5 microM EIPA, a NHE-1-specific inhibitor, prevented ouabain-mediated stimulation of (86)Rb uptake and Na-K-ATPase phosphorylation in OK, HKC-5, and HKC-11 cells. Expression of wild-type NHE-1 in HK2 cells restored regulation of Na-K-ATPase by picomolar ouabain. Treatment with picomolar ouabain increased membrane expression of Na-K-ATPase and enhanced NHE-1-Na-K-ATPase alpha1-subunit association. Treatment with ouabain (1 microg x kg body wt(-1) x day(-1)) increased Na-K-ATPase activity, expression, phosphorylation, and association with NHE-1 increased in rat kidney cortical basolateral membranes. Eight days' treatment with ouabain (1 microg x kg body wt(-1) x day(-1)) resulted in increased blood pressure in these rats. These results suggest that the association of NHE-1 with Na-K-ATPase is critical for ouabain-mediated regulation of Na-K-ATPase and that these effects may play a role in cardioglycoside-stimulated hypertension.
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