ArticleAmerican journal of physiology. Cell physiology2013
Activation of c-SRC underlies the differential effects of ouabain and digoxin on Ca(2+) signaling in arterial smooth muscle cells.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Na/K-ATPase in the renal proximal tubule cell: classic & novel roles in sodium handling.Frontiers in physiology · 2026Review
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
- The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.Clinical science (London, England : 1979) · 2023Review
- Role of NaBulletin of experimental biology and medicine · 2023Article
- Augmented Ouabain-Induced Vascular Response Reduces Cardiac Efficiency in Mice with Migraine-Associated Mutation in the NaBiomedicines · 2023Article
- The microtubule network enables Src kinase interaction with the Na,K-ATPase to generate CaFrontiers in physiology · 2022Article
- Cardiac Oxidative Signaling and Physiological Hypertrophy in the Na/K-ATPase α1International journal of molecular sciences · 2021Article
- Ouabain Suppresses IL-6/STAT3 Signaling and Promotes Cytokine Secretion in Cultured Skeletal Muscle Cells.Frontiers in physiology · 2020Article
- Periplocymarin Plays an Efficacious Cardiotonic RoleFrontiers in pharmacology · 2020Article
- Smooth muscle CaJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019Article
- Ouabain Enhances Cell-Cell Adhesion Mediated by βInternational journal of molecular sciences · 2019Article
- NaAmerican journal of physiology. Heart and circulatory physiology · 2019Article
- NaAutism research : official journal of the International Society for Autism Research · 2018Article
- Telocinobufagin and Marinobufagin Produce Different Effects in LLC-PK1 Cells: A Case of Functional Selectivity of Bufadienolides.International journal of molecular sciences · 2018Article
- Cardiotonic Steroids and the Sodium Trade Balance: New Insights into Trade-Off Mechanisms Mediated by the Na⁺/K⁺-ATPase.International journal of molecular sciences · 2018Review
- The Na,K-ATPase-Dependent Src Kinase Signaling Changes with Mesenteric Artery Diameter.International journal of molecular sciences · 2018Article
- Central and peripheral slow-pressor mechanisms contributing to Angiotensin II-salt hypertension in rats.Cardiovascular research · 2018Article
- The pump, the exchanger, and the holy spirit: origins and 40-year evolution of ideas about the ouabain-NaAmerican journal of physiology. Cell physiology · 2018Review
- How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac NaAmerican journal of physiology. Heart and circulatory physiology · 2017Review
- Update on angiotensin II: new endocrine connections between the brain, adrenal glands and the cardiovascular system.Endocrine connections · 2017Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cardiotonic steroids (CTS) of the strophanthus and digitalis families have opposing effects on long-term blood pressure (BP). This implies hitherto unrecognized divergent signaling pathways for these CTS. Prolonged ouabain treatment upregulates Ca(2+) entry via Na(+)/Ca(2+) exchanger-1 (NCX1) and TRPC6 gene-encoded receptor-operated channels in mesenteric artery smooth muscle cells (ASMCs) in vivo and in vitro. Here, we test the effects of digoxin on Ca(2+) entry and signaling in ASMC. In contrast to ouabain treatment, the in vivo administration of digoxin (30 μg·kg(-1)·day(-1) for 3 wk) did not raise BP and had no effect on resting cytolic free Ca(2+) concentration ([Ca(2+)](cyt)) or phenylephrine-induced Ca(2+) signals in isolated ASMCs. Expression of transporters in the α2 Na(+) pump-NCX1-TRPC6 Ca(2+) signaling pathway was not altered in arteries from digoxin-treated rats. Upregulated α2 Na(+) pumps and a phosphorylated form of the c-SRC protein kinase (pY419-Src, ~4.5-fold) were observed in ASMCs from rats treated with ouabain but not digoxin. Moreover, in primary cultured ASMCs from normal rats, treatment with digoxin (100 nM, 72 h) did not upregulate NCX1 and TRPC6 but blocked the ouabain-induced upregulation of these transporters. Pretreatment of ASMCs with the c-Src inhibitor PP2 (1 μM; 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine) but not its inactive analog eliminated the effect of ouabain on NCX1 and TRPC6 expression and ATP-induced Ca(2+) entry. Thus, in contrast to ouabain, the interaction of digoxin with α2 Na(+) pumps is unable to activate c-Src phosphorylation and upregulate the downstream NCX1-TRPC6 Ca(2+) signaling pathway in ASMCs. The inability of digoxin to upregulate c-Src may underlie its inability to raise long-term BP.
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