ouabain

Summary

Summary: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.

Top Publications

  1. pmc Naloxone and ouabain in ultralow concentrations restore Na+/K+-ATPase and cytoskeleton in lipopolysaccharide-treated astrocytes
    Johan Forshammar
    Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, 1tr, SE 413 45, Gothenburg, Sweden
    J Biol Chem 286:31586-97. 2011
  2. ncbi The alpha2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro
    Iva Dostanic
    Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA
    Am J Physiol Heart Circ Physiol 288:H477-85. 2005
  3. pmc Changes in sodium pump expression dictate the effects of ouabain on cell growth
    Jiang Tian
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA
    J Biol Chem 284:14921-9. 2009
  4. ncbi Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth
    Wilhelm Schoner
    Institut für Biochemie und Endokrinologie, Fachbereich Veterinarmedizin, Justus Liebig Universitat Giessen, Frankfurter Str 100, Giessen, Germany
    Am J Physiol Cell Physiol 293:C509-36. 2007
  5. pmc Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site
    Mette Laursen
    Centre for Membrane Pumps in Cells and Disease PUMPKIN, Danish National Research Foundation, DK 8000 Aarhus C, Denmark
    Proc Natl Acad Sci U S A 110:10958-63. 2013
  6. ncbi Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets
    Mariko Kajikawa
    Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Diabetes 51:2522-9. 2002
  7. pmc Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo
    Bing Song
    Department of Biomedical Sciences, Institute of Medical Sciences, Medical School, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK
    Proc Natl Acad Sci U S A 99:13577-82. 2002
  8. ncbi A cytolytic assay for the measurement of palytoxin based on a cultured monolayer cell line
    Mirella Bellocci
    Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, I 41100 Modena, Italy
    Anal Biochem 374:48-55. 2008
  9. ncbi Neurogenic nitric oxide release increases in mesenteric arteries from ouabain hypertensive rats
    Fabiano E Xavier
    Departamentos de Fisiología and Farmacología y Terapéutica, Facultad de Medicina, Universidad Autonoma, C Arzobispo Morcillo 4, 28029 Madrid, Spain
    J Hypertens 22:949-57. 2004
  10. pmc Normal pregnancy: mechanisms underlying the paradox of a ouabain-resistant state with elevated endogenous ouabain, suppressed arterial sodium calcium exchange, and low blood pressure
    Brandiese E Jacobs
    Department of Physiology, School of Medicine, University of Maryland, Baltimore, USA
    Am J Physiol Heart Circ Physiol 302:H1317-29. 2012

Detail Information

Publications354 found, 100 shown here

  1. pmc Naloxone and ouabain in ultralow concentrations restore Na+/K+-ATPase and cytoskeleton in lipopolysaccharide-treated astrocytes
    Johan Forshammar
    Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, 1tr, SE 413 45, Gothenburg, Sweden
    J Biol Chem 286:31586-97. 2011
    ..Naloxone and ouabain were tested separately in ultralow or high concentrations...
  2. ncbi The alpha2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro
    Iva Dostanic
    Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA
    Am J Physiol Heart Circ Physiol 288:H477-85. 2005
    Although ouabain is known to induce hypertension, the mechanism of how this cardiac glycoside affects blood pressure is uncertain...
  3. pmc Changes in sodium pump expression dictate the effects of ouabain on cell growth
    Jiang Tian
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA
    J Biol Chem 284:14921-9. 2009
    Here we show that ouabain-induced cell growth regulation is intrinsically coupled to changes in the cellular amount of Na/K-ATPase via the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway...
  4. ncbi Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth
    Wilhelm Schoner
    Institut für Biochemie und Endokrinologie, Fachbereich Veterinarmedizin, Justus Liebig Universitat Giessen, Frankfurter Str 100, Giessen, Germany
    Am J Physiol Cell Physiol 293:C509-36. 2007
    ..Among them are the hydrophilic cardenolide ouabain and the more hydrophobic cardenolide digoxin, as well as the bufadienolides marinobufagenin and telecinobufagin...
  5. pmc Crystal structure of the high-affinity Na+K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site
    Mette Laursen
    Centre for Membrane Pumps in Cells and Disease PUMPKIN, Danish National Research Foundation, DK 8000 Aarhus C, Denmark
    Proc Natl Acad Sci U S A 110:10958-63. 2013
    ..a crystal structure of the phosphorylated pig kidney Na(+),K(+)-ATPase in complex with the CTS representative ouabain, extending to 3.4 Å resolution...
  6. ncbi Ouabain suppresses glucose-induced mitochondrial ATP production and insulin release by generating reactive oxygen species in pancreatic islets
    Mariko Kajikawa
    Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Diabetes 51:2522-9. 2002
    ..b>Ouabain, an inhibitor of Na(+)/K(+)-ATPase, augmented 16...
  7. pmc Electrical cues regulate the orientation and frequency of cell division and the rate of wound healing in vivo
    Bing Song
    Department of Biomedical Sciences, Institute of Medical Sciences, Medical School, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK
    Proc Natl Acad Sci U S A 99:13577-82. 2002
    ..Because the endogenous EF also regulated the wound healing rate, it may act as one control of the interplay between cell migration and cell division during healing...
  8. ncbi A cytolytic assay for the measurement of palytoxin based on a cultured monolayer cell line
    Mirella Bellocci
    Dipartimento di Scienze Biomediche, Universita di Modena e Reggio Emilia, I 41100 Modena, Italy
    Anal Biochem 374:48-55. 2008
    ..for this group of compounds, acting on Na+/K+-ATPase, as it was prevented when cells were preincubated with ouabain. The specificity of our assay for palytoxin and its congeners was confirmed by the finding that cytolysis was not ..
  9. ncbi Neurogenic nitric oxide release increases in mesenteric arteries from ouabain hypertensive rats
    Fabiano E Xavier
    Departamentos de Fisiología and Farmacología y Terapéutica, Facultad de Medicina, Universidad Autonoma, C Arzobispo Morcillo 4, 28029 Madrid, Spain
    J Hypertens 22:949-57. 2004
    We investigated whether chronic ouabain treatment changes the vasoconstrictor responses induced by electrical field stimulation (EFS) in endothelium-denuded rat superior mesenteric arteries and a possible role of neuronal nitric oxide (..
  10. pmc Normal pregnancy: mechanisms underlying the paradox of a ouabain-resistant state with elevated endogenous ouabain, suppressed arterial sodium calcium exchange, and low blood pressure
    Brandiese E Jacobs
    Department of Physiology, School of Medicine, University of Maryland, Baltimore, USA
    Am J Physiol Heart Circ Physiol 302:H1317-29. 2012
    ..Here we test the hypothesis that vascular resistance to endogenous ouabain (EO) develops in normal pregnancy and is mediated by reduced expression of NCX1.3 and TRPCs...
  11. pmc Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase
    H Hiyoshi
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm SE 17177, Sweden
    Br J Cancer 106:1807-15. 2012
    ..The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through ..
  12. ncbi Palytoxin detection and quantification using the fluorescence polarization technique
    A Alfonso
    Department of Pharmacology, Veterinary School, 27002 Lugo, Spain
    Anal Biochem 424:64-70. 2012
    ..The assay protocol was first developed using ouabain as a binding molecule. The final result was a straight line that correlates FP units and PLT concentration...
  13. pmc Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain
    Haruo Ogawa
    Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo ku, Tokyo 113 0032, Japan
    Proc Natl Acad Sci U S A 106:13742-7. 2009
    ..Here we describe a crystal structure of Na(+),K(+)-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 A resolution in a state analogous to E2.2K(+).Pi...
  14. ncbi Apoptosis-mediated cytotoxicity of ouabain, digoxin and proscillaridin A in the estrogen independent MDA-MB-231 breast cancer cells
    Katarzyna Winnicka
    Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University in Bialystok, Kilinskiego 1, 15 089 Bialystok, Poland
    Arch Pharm Res 30:1216-24. 2007
    We examined the effects of three cardiac glycosides, ouabain, digoxin and proscillaridin A, on the proliferation of estrogen independent MDA-MB-231 breast cancer cells...
  15. pmc Differential effects of Na+-K+ ATPase blockade on cortical layer V neurons
    Trent R Anderson
    Neurology and Neurological Sciences, Stanford University, CA 94305, USA
    J Physiol 588:4401-14. 2010
    ..Bath perfusion of Na(+)-K(+) ATPase antagonists (ouabain or dihydro-ouabain) induced either a membrane depolarization in current clamp, or inward current under voltage ..
  16. pmc Ouabain modulates epithelial cell tight junction
    Isabel Larre
    Department of Physiology, Center for Research and Advanced Studies, 07300 Mexico DF, Mexico
    Proc Natl Acad Sci U S A 107:11387-92. 2010
    Epithelial cells treated with high concentrations of ouabain (e.g., 1 microM) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates...
  17. ncbi Intracellular reactive oxygen species mediate the linkage of Na+/K+-ATPase to hypertrophy and its marker genes in cardiac myocytes
    Z Xie
    Departments of Pharmacology and Medicine, Medical College of Ohio, Toledo, Ohio 43614, USA
    J Biol Chem 274:19323-8. 1999
    We showed before that in cardiac myocytes partial inhibition of Na+/K+-ATPase by nontoxic concentrations of ouabain causes hypertrophy and transcriptional regulations of growth-related marker genes through multiple Ca2+-dependent signal ..
  18. ncbi Ouabain-like compound changes rapidly on physical exercise in humans and dogs: effects of beta-blockade and angiotensin-converting enzyme inhibition
    Natali Bauer
    Clinic for Small Animal Internal Medicine and Forensic Affairs, Faculty of Veterinary Medicine, Justus Liebig University Giessen, Germany
    Hypertension 45:1024-8. 2005
    b>Ouabain, an inhibitor of the sodium pump, has been identified as a constituent of bovine adrenal glands. We were interested whether the release of this cardiotonic steroid is stimulated by physical exercise...
  19. ncbi Ouabain interaction with cardiac Na/K-ATPase reveals that the enzyme can act as a pump and as a signal transducer
    Z Xie
    Department of Pharmacology, Medical College of Ohio, Toledo 43614 5804, USA
    Cell Mol Biol (Noisy-le-grand) 47:383-90. 2001
    ..gradients of Na+ and K+ found in most mammalian cells and is inhibited specifically by cardiac glycosides such as ouabain. Recently, we have shown that partial inhibition of Na/K-ATPase by non-toxic concentrations of ouabain causes ..
  20. pmc Ouabain, a steroid hormone that signals with slow calcium oscillations
    O Aizman
    Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children's Hospital, Q2:09, S-171 76 Stockholm, Sweden
    Proc Natl Acad Sci U S A 98:13420-4. 2001
    ..Recent studies demonstrate the presence of a digoxin analog, ouabain, in mammalian tissue, but its biological role has not been elucidated...
  21. pmc Differential expression of Na+/K+-ATPase alpha-subunits in mouse hippocampal interneurones and pyramidal cells
    Kathryn S Richards
    INSERM U739, CHU Pitie Salpetriere, 105 Boulevard de l Hôpital, 75013 Paris, France
    J Physiol 585:491-505. 2007
    ..We used the sensitivity to the cardiac glycoside, ouabain, to discriminate between different alpha subunit isoforms...
  22. pmc Endogenous cardiotonic steroids: physiology, pharmacology, and novel therapeutic targets
    Alexei Y Bagrov
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA
    Pharmacol Rev 61:9-38. 2009
    ..Recent discoveries, which include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of an alternative mechanism by ..
  23. ncbi Regeneration of inner retinal neurons after intravitreal injection of ouabain in zebrafish
    Shane M Fimbel
    Department of Biological Sciences and Center for Zebrafish Research, University of Notre Dame, Notre Dame, Indiana 46556, USA
    J Neurosci 27:1712-24. 2007
    We examined the regenerative capacity of the adult zebrafish retina by intravitreal injection of a low ouabain concentration to rapidly damage the ganglion cell layer (GCL) and inner nuclear layer (INL) with minimal photoreceptor cell ..
  24. ncbi Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells
    Peter Kometiani
    Department of Pharmacology, Medical College of Ohio, 3035 Arlington Ave, Toledo, OH 43614 5804, USA
    Mol Pharmacol 67:929-36. 2005
    ..b>Ouabain concentrations (100 nM or lower) that caused less than 25% inhibition of the pumping function of Na+/K+-ATPase ..
  25. pmc Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity
    Ronald J Y Chen
    Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan, China
    Acta Pharmacol Sin 30:61-9. 2009
    ..as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin.
  26. pmc Alcohol excites cerebellar Golgi cells by inhibiting the Na+/K+ ATPase
    Paolo Botta
    Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 0001, USA
    Neuropsychopharmacology 35:1984-96. 2010
    ..indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of ouabain. Partial inhibition of Na(+)/K(+) ATPase function in a computer model of the Golgi cell reproduced these ..
  27. ncbi Left ventricular mass, stroke volume, and ouabain-like factor in essential hypertension
    P Manunta
    University of Milan and Division of Nephrology, Dialysis and Hypertension, IRCCS San Raffaele Hospital, Milan, Italy
    Hypertension 34:450-6. 1999
    ..Moreover, ouabain has a hypertrophic influence on isolated cardiac myocytes...
  28. ncbi New roles for an old enzyme: Na,K-ATPase emerges as an interesting drug target
    A Aperia
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden
    J Intern Med 261:44-52. 2007
    ..The signal transduction function can be triggered by the binding of ouabain, the mammalian analogue of digitalis to NKA...
  29. ncbi Ouabain induces endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1 cells by a clathrin-dependent mechanism
    Jiang Liu
    The Department of Medicine, Medical College of Ohio, Toledo, Ohio, USA
    Kidney Int 66:227-41. 2004
    We have demonstrated that ouabain causes dose- and time-dependent decreases in (86)Rb uptake in porcine proximal tubular (LLC-PK1) cells. The present study addresses the molecular mechanisms involved in this process.
  30. ncbi Palytoxin-induced cell death cascade in bovine aortic endothelial cells
    William P Schilling
    Rammelkamp Center for Education and Research, MetroHealth Medical Center, Cleveland, OH 44109 1998, USA
    Am J Physiol Cell Physiol 291:C657-67. 2006
    ..The increase in [Ca(2+)](i) initiated by 100 nM PTX was blocked by pretreatment with ouabain with an IC(50) < 1 microM...
  31. ncbi Digoxin and ouabain induce the efflux of cholesterol via liver X receptor signalling and the synthesis of ATP in cardiomyocytes
    Ivana Campia
    Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
    Biochem J 447:301-11. 2012
    ..We showed previously that in human hepatoma cells, digoxin and ouabain increase the rate of the mevalonate cascade and therefore have Na(+)/K(+)-ATPase-independent effects...
  32. pmc Modulation of cardiac Na+,K+-ATPase cell surface abundance by simulated ischemia-reperfusion and ouabain preconditioning
    Aude Belliard
    Department of Biochemistry, College of Medicine, University of Toledo, 3000 Arlington Ave, Toledo, OH 43614, USA
    Am J Physiol Heart Circ Physiol 304:H94-103. 2013
    ..survival were investigated in a cellular model of ischemia-reperfusion (I/R)-induced injury and protection by ouabain-induced preconditioning (OPC)...
  33. ncbi Positive inotropic effect of ouabain on isolated heart is accompanied by activation of signal pathways that link Na+/K+-ATPase to ERK1/2
    Kamiar Mohammadi
    Department of Pharmacology, Medical College of Ohio, Toledo, Ohio, 43614 5804, USA
    J Cardiovasc Pharmacol 41:609-14. 2003
    Exposure of cultured rat cardiac myocytes to ouabain is known to cause the interaction of Na+/K+-ATPase with adjacent proteins, leading to activation of multiple signal transduction pathways, regulation of growth-related genes, and ..
  34. ncbi Antiproliferative activity of derivatives of ouabain, digoxin and proscillaridin A in human MCF-7 and MDA-MB-231 breast cancer cells
    Katarzyna Winnicka
    Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego, Bialystok, Poland
    Biol Pharm Bull 31:1131-40. 2008
    Three derivatives of ouabain, digoxin and proscillaridin A containing the carboxylic group instead of the lactone moiety were synthesized and examined for cytotoxicity in human breast cancer cells...
  35. pmc Endogenous concentrations of ouabain act as a cofactor to stimulate fluid secretion and cyst growth of in vitro ADPKD models via cAMP and EGFR-Src-MEK pathways
    Kyle Jansson
    Dept of Molecular and Integrative Physiology, 3901 Rainbow Blvd, Kansas City, KS 66160, USA
    Am J Physiol Renal Physiol 303:F982-90. 2012
    ..We previously showed that ouabain increases proliferation of cultured human ADPKD cells via stimulation of the EGF receptor (EGFR)-Src-MEK/ERK ..
  36. ncbi Skeletal muscle ouabain binding sites are reduced in rats with chronic heart failure
    Timothy I Musch
    Department of Anatomy, Kansas State University, Manhattan, Kansas 66506 5802, USA
    J Appl Physiol (1985) 92:2326-34. 2002
    ..In CHF patients, the number of skeletal muscle Na(+)-K(+) pumps that have a high affinity for ouabain (i.e...
  37. ncbi Ouabain is a potent promoter of growth and activator of ERK1/2 in ouabain-resistant rat renal epithelial cells
    Renata I Dmitrieva
    Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA
    J Biol Chem 278:28160-6. 2003
    ..We investigated four parameters to determine whether ouabain, a proposed ECS, promotes growth of immortalized rat proximal tubule epithelial cells: cell count by ..
  38. pmc Ouabain modulates ciliogenesis in epithelial cells
    Isabel Larre
    Department of Physiology, Biophysics and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute, Mexico City, DF 07300, Mexico
    Proc Natl Acad Sci U S A 108:20591-6. 2011
    ..In a previous study, we demonstrated that 10 nM ouabain modulates TJs, and we now show that it controls polarity as well...
  39. pmc Salt sensitivity, endogenous ouabain and hypertension
    John M Hamlyn
    Department of Physiology, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA
    Curr Opin Nephrol Hypertens 22:51-8. 2013
    ..Here we discuss recent observations on mechanisms of salt sensitivity that involve endogenous ouabain and novel pathways in the brain and discuss their possible relationship to arterial and renal function in ..
  40. ncbi Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors
    Luciana V Rossoni
    Department of Pharmacology and Therapeutics, Faculty of Medicine, Autonomous University of Madrid, C Arzobispo Morcillo 4, 28029 Madrid, Spain
    Am J Physiol Heart Circ Physiol 283:H2110-8. 2002
    ..contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension...
  41. ncbi Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells
    D J McConkey
    Department of Cancer Biology, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Cancer Res 60:3807-12. 2000
    ..Here, we report that the cardiac glycosides oleandrin, ouabain, and digoxin induce apoptosis in androgen-independent human prostate cancer cell lines in vitro...
  42. pmc Ouabain-induced cochlear degeneration in rat
    Yong Fu
    Department of Otorhinolaryngology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China
    Neurotox Res 22:158-69. 2012
    b>Ouabain, a potent inhibitor of the Na+/K+-ATPase pump, selectively destroys spiral ganglion neurons (SGNs) in gerbils and mice, whereas in guinea pigs it preferentially damages cochlear hair cells...
  43. ncbi Ouabain activates signaling pathways associated with cell death in human neuroblastoma
    Andrey Kulikov
    Institut für Biochemie und Endokrinologie, Fachbereich Veterinarmedizin, Justus Liebig Universität Frankfurter Str 100, D 35392 Giessen, Germany
    Biochim Biophys Acta 1768:1691-702. 2007
    Cardiotonic steroids (CTS) like ouabain are not only specific inhibitors of the sodium pump (Na(+),K(+)-ATPase), they also can influence various cytosolic signaling events in a hormone-like manner...
  44. ncbi Ouabain assembles signaling cascades through the caveolar Na+/K+-ATPase
    Haojie Wang
    Department of Pharmacology and Medicine, Medical College of Ohio, Toledo, Ohio 43614, USA
    J Biol Chem 279:17250-9. 2004
    ..motifs, we hypothesized that clustering of the Na(+)/K(+)-ATPase and its partners in caveolae facilitates ouabain-activated signal transduction...
  45. pmc Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat
    Chunhua Cao
    Department of Medicine, UMMS, Baltimore, MD 21201, USA
    Am J Physiol Renal Physiol 296:F98-F106. 2009
    Descending vasa recta (DVR) are 15-microm vessels that perfuse the renal medulla. Ouabain has been shown to augment DVR endothelial cytoplasmic Ca(2+) ([Ca(2+)](CYT)) signaling...
  46. pmc Sox2 up-regulation and glial cell proliferation following degeneration of spiral ganglion neurons in the adult mouse inner ear
    Hainan Lang
    Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Avenue, Charleston, SC 29425, USA
    J Assoc Res Otolaryngol 12:151-71. 2011
    ..b>Ouabain, a well-known Na,K-ATPase inhibitor, has been shown to induce SGN degeneration while sparing hair cell function...
  47. ncbi Long-term ouabain treatment impairs vascular function in resistance arteries
    Camilla Ferreira Wenceslau
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
    J Vasc Res 48:316-26. 2011
    The purpose of this study was to examine the cardiovascular effects of long-term ouabain treatment at different time points.
  48. pmc Large diameter of palytoxin-induced Na/K pump channels and modulation of palytoxin interaction by Na/K pump ligands
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021 6399, USA
    J Gen Physiol 123:357-76. 2004
    ..5 A wide. Enhanced understanding of palytoxin action now allows its use for examining the structures and mechanisms of the gates that occlude/deocclude transported ions during the normal Na/K pump cycle...
  49. pmc Ouabain binding site in a functioning Na+/K+ ATPase
    Walter Sandtner
    Department of Pharmacology, Medical University of Vienna, Waehringer Strasse 13a, 1090 Vienna, Austria
    J Biol Chem 286:38177-83. 2011
    ..Functional studies revealed that ouabain-sensitive residues distributed widely throughout the primary sequence of the protein...
  50. ncbi The cytotoxic effect of palytoxin on Caco-2 cells hinders their use for in vitro absorption studies
    M Pelin
    Department of Life Sciences, University of Trieste, via Valerio 6, 34127 Trieste, Italy
    Food Chem Toxicol 50:206-11. 2012
    ..These results indicate that, due to the high susceptibility to PLTX cytotoxic effects, Caco-2 cells do not represent an appropriate and reliable model for investigating intestinal barrier permeation by this toxin...
  51. ncbi Study of the neuronal effects of ouabain and palytoxin and their binding to Na,K-ATPases using an optical biosensor
    C Vale-Gonzalez
    Departamento de Farmacologia, Universidad de Santiago de Compostela, Campus Universitario s n 27002 Lugo, Spain
    Toxicon 50:541-52. 2007
    ..Ca2+]i) and intracellular pH (pH(i)) in primary cultures of cerebellar granule cells (CGC) and compared PTX and ouabain actions in the same cellular parameters...
  52. ncbi Antineoplastic activity of ouabain and pyrithione zinc in acute myeloid leukemia
    M Tailler
    INSERM, U848, Villejuif, France
    Oncogene 31:3536-46. 2012
    ..Among a panel of 1040 Food and Drug Administration-approved agents, we identified pyrithione zinc (PZ) and ouabain (OUA) as potential antileukemic compounds...
  53. pmc Ouabain affinity determining residues lie close to the Na/K pump ion pathway
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:12613-8. 2006
    ..Cardiotonic steroids, such as ouabain, are specific inhibitors of the Na/K pump...
  54. ncbi Na+/K+ -ATPase regulates tight junction formation and function during mouse preimplantation development
    Michelle I Violette
    Department of Physiology and Pharmacology, The University of Western Ontario, The Children s Health Research Institute Victoria Research Laboratories, 800 Commissioners Road, London, Ontario, Canada N6A 4G5
    Dev Biol 289:406-19. 2006
    ..The first experiments defined the optimal dose and treatment time intervals for ouabain (a potent and specific inhibitor of the Na(+)/K(+)-ATPase) treatment...
  55. pmc Upregulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain-induced hypertensive rats
    Maria V Pulina
    Department of Physiology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
    Am J Physiol Heart Circ Physiol 298:H263-74. 2010
    Prolonged ouabain administration (25 microg kg(-1) day(-1) for 5 wk) induces "ouabain hypertension" (OH) in rats, but the molecular mechanisms by which ouabain elevates blood pressure are unknown...
  56. ncbi Ouabain binds with high affinity to the Na,K-ATPase in human polycystic kidney cells and induces extracellular signal-regulated kinase activation and cell proliferation
    Anh Nguyet T Nguyen
    Department of Molecular and Integrative Physiology, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
    J Am Soc Nephrol 18:46-57. 2007
    ..Na,K-ATPase is essential for solute and water transport in ADPKD cells, and ouabain blocks fluid secretion in these cells...
  57. ncbi Investigation of ouabain-induced anticancer effect in human androgen-independent prostate cancer PC-3 cells
    Yao Ting Huang
    Pharmacological Institute, College of Medicine, National Taiwan University, No 1, Jen Ai Road, sect 1, Taipei, Taiwan, ROC
    Biochem Pharmacol 67:727-33. 2004
    To determine the therapeutic potential of cardiac glycosides in androgen-independent prostate cancer, we examined ouabain-induced cytotoxic effect as well as the signaling pathways in PC-3 cells...
  58. ncbi Increase in ouabain-sensitive K+-ATPase activity in hepatocellular carcinoma by overexpression of Na+, K+-ATPase alpha 3-isoform
    Kazuto Shibuya
    Department of Surgery II, Toyama 930 0194, Japan
    Eur J Pharmacol 638:42-6. 2010
    ..The ouabain (10 microM)-sensitive K(+)-ATPase activities (Na(+),K(+)-ATPase activities) in the membrane fraction from HCC ..
  59. ncbi Effects of aging and ouabain on left atrial arrhythmogenicity
    Wanwarang Wongcharoen
    National Yang Ming University, School of Medicine, Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital Taipei, Taipei, Taiwan
    J Cardiovasc Electrophysiol 18:526-31. 2007
    ..The purpose of this study was to evaluate the effects of aging on the LA electrophysiological heterogeneity and ouabain-induced arrhythmogenicity.
  60. ncbi Entamoeba histolytica: ouabain-insensitive Na(+)-ATPase activity
    Aloa M De Souza
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941 902 Rio de Janeiro, RJ, Brazil
    Exp Parasitol 117:195-200. 2007
    ..It is shown through the measurement of ouabain-sensitive ATPase activity and immunoblotting that E. histolytica does not express (Na(+)+K(+))ATPase...
  61. ncbi Src-mediated inter-receptor cross-talk between the Na+/K+-ATPase and the epidermal growth factor receptor relays the signal from ouabain to mitogen-activated protein kinases
    Michael Haas
    Department of Pharmacology, Medical College of Ohio, Toledo, Ohio 43614, USA
    J Biol Chem 277:18694-702. 2002
    Binding of ouabain to Na(+)/K(+)-ATPase activates tyrosine phosphorylation of the epidermal growth factor receptor (EGFR), Src, and p42/44 mitogen-activated protein kinases (MAPKs) in both cardiac myocytes and A7r5 cells...
  62. ncbi Dual effects of ouabain on the regulation of proliferation and apoptosis in human prostatic smooth muscle cells
    S C Chueh
    Department of Urology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
    J Urol 166:347-53. 2001
    PURPOSE: To elucidate the role of ouabain in the pathophysiology of benign prostatic hyperplasia we examined the effects of ouabain on the proliferation and apoptosis of human prostatic smooth muscle cells...
  63. ncbi Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype
    Lijun Liu
    Section of Cardiovascular Science, Dept of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Am J Physiol Heart Circ Physiol 287:H2173-82. 2004
    We have shown earlier that low concentrations of ouabain that do not perturb the ionic milieu can initiate proliferation of vascular smooth muscle cells (VSMCs) in the synthetic phenotype from three different species: canine, rodent, and ..
  64. ncbi Ouabain binding to Na+,K+-ATPase relaxes cell attachment and sends a specific signal (NACos) to the nucleus
    R G Contreras
    Department of Physiology, Biophysics and Neurosciences, Av, Center for Research and Advanced Studies, Instituto Politecnico Nacional 2508, 07300, Mexico, D F, Mexico
    J Membr Biol 198:147-58. 2004
    Abstract. In previous work we described a "P-->A mechanism" that transduces occupancy of the pump ( P) by ouabain into changes in phosphorylation, stimulation of mitogen-activated protein kinase (MAPK), and endocytosis of cell-cell- ..
  65. ncbi Death of ouabain-treated renal epithelial cells: evidence for p38 MAPK-mediated Na (i) (+) /K (i) (+) -independent signaling
    Olga A Akimova
    Centre de Recherche, Centre Hospitalier de l Universite de Montreal, QC, Canada
    Apoptosis 14:1266-73. 2009
    Recent studies demonstrate that cytotoxic actions of ouabain and other cardiotonic steroids (CTS) on renal epithelial cells (REC) are triggered by their interaction with the Na(+),K(+)-ATPase alpha-subunit but not the result of ..
  66. ncbi Mechanisms of ouabain toxicity
    Raphael C Valente
    Departamento de Bioquimica Medica, Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro UFRJ, Brazil
    FASEB J 17:1700-2. 2003
    The suggested involvement of ouabain in hypertension raised the need for a better understanding of its cellular action, but the mechanisms of ouabain toxicity are only now being uncovered...
  67. ncbi Ouabain-insensitive Na+-ATPase of proximal tubules is an effector for urodilatin and atrial natriuretic peptide
    C Caruso-Neves
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS Bloco G, 21949 900 Rio de Janeiro, RJ, Brazil
    Biochim Biophys Acta 1660:93-8. 2004
    ..The data obtained indicate that this effect is mediated by the activation of the NPR-A/guanylate cyclase/cGMP pathway...
  68. pmc Resolution of the insect ouabain paradox
    Leah S Torrie
    Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, Scotland, United Kingdom
    Proc Natl Acad Sci U S A 101:13689-93. 2004
    Many insects are highly resistant to plant toxins, such as the cardiac glycoside ouabain. How can the epithelia that must handle such toxins, also be refractory to them? In Drosophila, the Malpighian (renal) tubule contains large amounts ..
  69. pmc Frequency spectrum of transepithelial potential difference reveals transport-related oscillations
    Nicolás Montalbetti
    Institute of Cardiology Research, University of Buenos Aires, and CONICET, Buenos Aires, Argentina
    Biophys J 97:1530-7. 2009
    ....
  70. pmc Dysfunction of ouabain-induced cardiac contractility in mice with heart-specific ablation of Na,K-ATPase beta1-subunit
    Sonali P Barwe
    Nemours Center for Childhood Cancer Research, Alfred I duPont Hospital for Children, Rockland Center One, 1701 Rockland Road, Wilmington, DE 19803, USA
    J Mol Cell Cardiol 47:552-60. 2009
    ..that intact hearts of Na,K-beta(1) KO anesthetized mice as well as isolated cardiomyocytes were insensitive to ouabain-induced positive inotropy...
  71. ncbi Endogenous ouabain in cardiovascular function and disease
    Paolo Manunta
    San Raffaele Scientific Institute, Division of Nephrology, Dialysis, and Hypertension, Universita Vita Salute San Raffaele Hospital, Milan, Italy
    J Hypertens 27:9-18. 2009
    An endogenous ouabain has been isolated and conclusively identified from several mammalian tissues, including human plasma, by a number of independent laboratories...
  72. ncbi Na(+)-ATPase in spontaneous hypertensive rats: possible AT(1) receptor target in the development of hypertension
    Eugênio P Queiroz-Madeira
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS Bloco G, 21949 900 Rio de Janeiro, RJ, Brazil
    Biochim Biophys Acta 1798:360-6. 2010
    ..The present study was designed to examine ouabain-insensitive Na(+)-ATPase activity and its regulation by Ang II in spontaneously hypertensive rats (SHR)...
  73. ncbi Isolation and cloning of the K+-independent, ouabain-insensitive Na+-ATPase
    Miguel A Rocafull
    Laboratorio de Fisiología Molecular, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela
    Biochim Biophys Acta 1808:1684-700. 2011
    ..However, there are functional and biochemical evidences that suggest the existence of a K+-independent, ouabain-insensitive Na+ pump, associated to a Na+-ATPase with similar characteristics, located at basolateral plasma ..
  74. ncbi Ouabain-resistant OR6 cells express the murine alpha 1-subunit of the Na,K-ATPase with a T797-I797 substitution
    L G Cantley
    Division of Nephrology, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215
    J Biol Chem 269:15358-61. 1994
    Introduction of the murine "ouabain resistance gene" (Levenson, R., Racaniello, V., Albritton, L., and Housman, D. (1984) Proc. Natl. Acad. Sci. U.S.A...
  75. ncbi The sodium pump and cardiotonic steroids-induced signal transduction protein kinases and calcium-signaling microdomain in regulation of transporter trafficking
    Jiang Liu
    Department of Medicine, University of Toledo College of Medicine, Toledo, OH, USA
    Biochim Biophys Acta 1802:1237-45. 2010
    ..The plant-derived CTS such as digoxin are valuable drugs for the management of cardiac diseases, whereas ouabain and marinobufagenin (MBG) have been identified as a new class of endogenous hormones...
  76. ncbi Phosphorylated intermediate of the ouabain-insensitive, Na(+)-stimulated ATPase in rat kidney cortex and rainbow trout gills
    V Ventrella
    Department of Biochemistry G Moruzzi, University of Bologna, BO, Italy
    Biochimie 92:128-35. 2010
    Several tissues from different animals, including the rat kidney and the freshwater rainbow trout gills, show an ouabain-insensitive, furosemide-sensitive, Na(+)-stimulated ATPase activity, which has been associated with the active ..
  77. ncbi Circulating endogenous digitalis-like factor(s) (EDLF) in man is derived from the adrenals and its secretion is ACTH-dependent
    A Sophocleous
    Section of Biochemistry and Molecular Biology, Department of Biology, University of Athens, Athens, Greece
    J Endocrinol Invest 26:668-74. 2003
    ..reactivity was monitored in plasma extracts (combined organic solvent solid phase method) by digoxin and ouabain radioimmunoassay (RIAD and RIAO, respectively)...
  78. ncbi Ouabain, a new steroid hormone of adrenal gland and hypothalamus
    W Schoner
    Institut für Biochemie und Endokrinologie, Justus Liebig Universitat Giessen
    Exp Clin Endocrinol Diabetes 108:449-54. 2000
    b>Ouabain has been isolated and identified as a constituent of human blood, bovine adrenal glands and hypothalamus...
  79. ncbi Reconstruction of the complete ouabain-binding pocket of Na,K-ATPase in gastric H,K-ATPase by substitution of only seven amino acids
    Li Yan Qiu
    Department of Biochemistry 160, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
    J Biol Chem 280:32349-55. 2005
    ..we started from the fact that a closely related enzyme, the gastric H,K-ATPase, does not bind glycosides like ouabain. Previously, we showed that a chimera of these two enzymes, in which only the M3-M4 and M5-M6 hairpins were of Na,..
  80. pmc Endogenous cardiotonic steroids and salt-sensitive hypertension
    Olga V Fedorova
    National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
    Biochim Biophys Acta 1802:1230-6. 2010
    ..Recent findings include the specific identification of endogenous cardenolide (endogenous ouabain) and bufadienolide (marinobufagenin) CTS in humans along with the delineation of mechanisms by which CTS can ..
  81. ncbi Regulation of apical NHE3 trafficking by ouabain-induced activation of the basolateral Na+-K+-ATPase receptor complex
    Haiping Cai
    Department of Medicine, University of Toledo College of Medicine, 3120 Glendale Ave, Toledo, OH 43614 5089, USA
    Am J Physiol Cell Physiol 294:C555-63. 2008
    The long-term effects of ouabain on transepithelial Na(+) transport involve transcriptional downregulation of apical Na(+)/H(+) exchanger isoform 3 (NHE3)...
  82. ncbi Ouabain induces cell proliferation through calcium-dependent phosphorylation of Akt (protein kinase B) in opossum kidney proximal tubule cells
    Syed J Khundmiri
    Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA
    Am J Physiol Cell Physiol 291:C1247-57. 2006
    Cardiotonic glycosides, like ouabain, inhibit Na(+)-K(+)-ATPase. Recent evidence suggests that low molar concentrations of ouabain alter cell growth...
  83. ncbi Organ hypertrophic signaling within caveolae membrane subdomains triggered by ouabain and antagonized by PST 2238
    Mara Ferrandi
    Prassis sigma tau Research Institute, Settimo Milanese, 20019 Milan, Italy
    J Biol Chem 279:33306-14. 2004
    In addition to inhibition of the Na-K ATPase, ouabain activates a signal transduction function, triggering growth and proliferation of cultured cells even at nanomolar concentrations...
  84. pmc The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase
    Jerry B Lingrel
    Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267 0524, USA
    Annu Rev Physiol 72:395-412. 2010
    ..This enzyme is highly sensitive to inhibition by cardiotonic steroids, most notably the digitalis/ouabain class of compounds, which have been used for centuries to treat congestive heart failure and arrhythmias...
  85. pmc Ionic mechanisms of cardiac cell swelling induced by blocking Na+/K+ pump as revealed by experiments and simulation
    Ayako Takeuchi
    Cell Biodynamics Simulation Project and Department of Physiology and Biophysics, Graduate School of Medicine, Kyoto University, Kyoto, 606 8501, Japan
    J Gen Physiol 128:495-507. 2006
    ..that cell volume remained almost constant during 90 min exposure of guinea pig ventricular myocytes to ouabain. Simulation of this finding using a comprehensive cardiac cell model (Kyoto model incorporating Cl(-) and water ..
  86. ncbi Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity and ouabain-induced arrhythmogenicity
    Wanwarang Wongcharoen
    National Yang Ming University, School of Medicine, Division of Cardiology, Veterans General Hospital Taipei, Taiwan
    Cardiovasc Res 70:497-508. 2006
    ..The purpose of this study was to investigate whether KB-R7943, a NCX current blocker with preferential inhibition of the Ca(2+) influx, may alter PV electrophysiological characteristics and reduce glycoside-induced arrhythmogenicity...
  87. ncbi Cell signaling microdomain with Na,K-ATPase and inositol 1,4,5-trisphosphate receptor generates calcium oscillations
    Ayako Miyakawa-Naito
    Department of Woman and Child Health, Karolinska Institutet, Astrid Lindgren Children s Hospital, S 171 76 Stockholm, Sweden
    J Biol Chem 278:50355-61. 2003
    ..We have previously demonstrated that ouabain, the endogenous ligand of Na,K-ATPase, can trigger intracellular Ca2+ oscillations, a versatile intracellular ..
  88. ncbi Characterization and partial isolation of ouabain-insensitive Na(+) -ATPase in MDCK I cells
    A M De Souza
    Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
    Biochimie 89:1425-32. 2007
    ..5) for Na(+) 7.5+/-1.5 mM and V(max) 23.12+/-1.1 nmol Pi/mg per min; (2) insensitive to 1 mM ouabain and 30 mM KCl; and (3) inhibited by furosemide and vanadate (IC(50) 42.1+/-8.0 and 4.3+/-0...
  89. ncbi Low doses of ouabain protect from serum deprivation-triggered apoptosis and stimulate kidney cell proliferation via activation of NF-kappaB
    Juan Li
    Karolinska Institutet, Department of Woman and Child Health, Astrid Lindgren Children s Hospital, Stockholm, Sweden
    J Am Soc Nephrol 17:1848-57. 2006
    ..It was reported recently that interaction between ouabain-bound Na,K-ATPase and the 1,4,5-trisphosphate receptor (IP3R) triggers slow calcium oscillations and activation ..
  90. ncbi The central role of the brain in salt-sensitive hypertension
    Bing S Huang
    Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada
    Curr Opin Cardiol 21:295-304. 2006
    ..To integrate recent studies showing that abnormal Na transport in the central nervous system plays a pivotal role in genetic models of salt-sensitive hypertension...
  91. ncbi Molecular mechanisms of Na/K-ATPase-mediated signal transduction
    Zijian Xie
    Department of Pharmacology and Medicine, Medical College of Ohio, Toledo 43614, USA
    Ann N Y Acad Sci 986:497-503. 2003
    Our recent work shows that in addition to pumping ions, Na/K-ATPase acts as a signal transducer. Binding of ouabain to Na/K-ATPase changes the interaction of the enzyme with neighboring membrane proteins and induces the formation of ..
  92. pmc Alterations in phenylephrine-induced contractions and the vascular expression of Na+,K+-ATPase in ouabain-induced hypertension
    Luciana V Rossoni
    Department of Pharmacology and Therapeutics, Facultad de Medicina, Universidad Autonoma de Madrid, Spain
    Br J Pharmacol 135:771-81. 2002
    ..functional activity and protein expression in aorta (AO), tail (TA) and superior mesenteric (SMA) arteries from ouabain- (25 microg day(-1), s.c., 5 weeks) and vehicle-treated rats were evaluated...
  93. ncbi Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump
    Robert Saunders
    Institut für Biochemie und Endokrinologie, Fachbereich Veterinarmedizin, Justus Liebig Universitat Giessen, Germany
    Eur J Biochem 271:1054-62. 2004
    b>Ouabain, a sodium pump (Na+/ K+-ATPase) inhibitor, has been shown to act as a hormone and is possibly involved in the pathogenesis of hypertension...
  94. ncbi Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain
    Luciano K Jornada
    Laboratory of Neurosciences and National Science and Technology Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88808 000 Criciúma, SC, Brazil
    J Psychiatr Res 44:506-10. 2010
    ..Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal ..
  95. ncbi Dual effects of ouabain, digoxin and proscillaridin A on the regulation of apoptosis in human fibroblasts
    Katarzyna Winnicka
    Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, 15 222 Bialystok, Poland
    Nat Prod Res 24:274-85. 2010
    In this study, we looked at the effect of ouabain, digoxin and proscillaridin A on human fibroblasts...
  96. ncbi Modulation of the immune system by ouabain
    Sandra Rodrigues-Mascarenhas
    Laboratorio de Tecnologia Farmaceutica, Departamento de Fisiologia e Patologia, Universidade Federal da Paraiba, Joao Pessoa, Brazil
    Ann N Y Acad Sci 1153:153-63. 2009
    b>Ouabain, a known inhibitor of the Na,K-ATPase, has been shown to regulate a number of lymphocyte functions in vitro and in vivo. Lymphocyte proliferation, apoptosis, cytokine production, and monocyte function are all affected by ouabain...
  97. ncbi Rostafuroxin: an ouabain-inhibitor counteracting specific forms of hypertension
    Patrizia Ferrari
    Prassis Research Institute sigma tau, Settimo M se, Milan, Italy
    Biochim Biophys Acta 1802:1254-8. 2010
    ..In the vasculature, it normalizes the increased myogenic tone caused by ouabain. A very high safety ratio and the absence of interaction with other mechanisms involved in BP regulation, ..
  98. ncbi Regulation of the sperm EGF receptor by ouabain leads to initiation of the acrosome reaction
    Limor Daniel
    The Mina and Everard Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel
    Dev Biol 344:650-7. 2010
    ..b>Ouabain, a known Na/K ATPase blocker is present in the blood and in the female reproductive tract...
  99. ncbi Inhibition of DNA topoisomerases I and II, and growth inhibition of breast cancer MCF-7 cells by ouabain, digoxin and proscillaridin A
    Krzysztof Bielawski
    Department of Medicinal Chemistry and Drug Technology, Medical University of Białystok, Poland
    Biol Pharm Bull 29:1493-7. 2006
    We evaluated the cytotoxicity and underlying mechanisms of cardiac glycosides, including digoxin, ouabain and proscillaridin A, on the proliferation of breast cancer MCF-7 cells...
  100. ncbi Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices
    M Balestrino
    Department of Neurological Sciences, University of Genova, Via De Toni 5, 16132, Genova GE, Italy
    Brain Res 838:37-44. 1999
    We used ouabain (100 microM) to block Na+,K(+)ATPase of in vitro rat hippocampal slices...
  101. ncbi Analysis of exercise-induced Na+-K+ exchange in rat skeletal muscle in vivo
    K T Murphy
    Institute of Phsiology and Biophysics, University of Aarhus, Arhus, Denmark
    Exp Physiol 93:1249-62. 2008
    ..Intracellular Na(+) and K(+) content, Na(+) permeability ((22)Na(+) influx), Na(+)-K(+) pump activity (ouabain-sensitive (86)Rb(+) uptake) and Na(+)-K(+) pump alpha(2) subunit content ([(3)H]ouabain binding) were measured...

Research Grants62

  1. REGULATION OF NA,K ATPASE BY THE AH RECEPTOR
    Mary Walker; Fiscal Year: 2004
    ..analysis of the avian gene; (2) determine the tissue significance of this regulation by quantitating myocardial ouabain binding sites and Na+/K+ ATPase enzyme activity in AhR null mice and TCDD-exposed chick embryos; (3) determine ..
  2. Endogenous Cardiac Glycosides in AASK
    Brad C Astor; Fiscal Year: 2010
    ..A new class of endogenous hormones, including ouabain and marinobufagenin, has recently been characterized...
  3. Ouabain, Na+ Pumps, and Ca2+ Signaling in Human Arteries
    Laura K Antos; Fiscal Year: 2010
    ..First, salt retention promotes secretion of the adrenocortical hormone, endogenous ouabain (EO)...
  4. Na,K-ATPase as an Integrator of the Calcium-signaling Machinery
    Zijian Xie; Fiscal Year: 2010
    ..between the Na/K-ATPase and other P-type ATPases is its ability to bind cardiotonic steroids (CIS) such as ouabain. While endogenous CTS regulate blood pressure via their effects on vasculature and renal salt handling, the plant-..
  5. Auditory Nerve Degeneration and Repair
    Hainan Lang; Fiscal Year: 2013
    ..at early post-injury intervals compared to later post-injury intervals using a well-characterized animal model of ouabain-induced acute SGN injury...
  6. Calcium and Sodium Transport in Hypertension
    John M Hamlyn; Fiscal Year: 2012
    ..We will employ pharmacological tools and genetically-engineered mice to test the hypothesis that: i) Endogenous ouabain (EO), ii) Inhibited activity of arterial Na+ pumps with a (ouabain-sensitive, S) [unreadable]2 catalytic subunit, ..
  7. Receptor Na/K-ATPase Antagonists As Novel Therapeutics For Renal/Cardiac Diseases
    Zijian Xie; Fiscal Year: 2013
    ..Finally, we have identified a novel class of small molecule antagonists that prevent ouabain from activating protein kinases in cell cultures. Therefore, we propose the following three specific aims...
  8. Phospholemman and Na-Pump Function in Cardiac Myocytes
    Donald M Bers; Fiscal Year: 2013
    ..Aim 3 examines questions that are inspired from our novel and surprising observation that ouabain abolishes FRET between NKA and either PLM or NKA...
  9. Elucidating the Role of Type II Afferent Neurons in Auditory Nociception
    EMMA NOEMI FLORES; Fiscal Year: 2013
    ..Using two animal models that have silenced type I afferents: (1) ouabain treated mice and (2) VGLUT3 KO mice, the proposal aims to determine the physiological activators of type II ..
  10. Alpha-2 Na+ Pumps, [Ca2+], Arterial Contraction &Hypertension
    Mordecai P Blaustein; Fiscal Year: 2013
    ..Extensive evidence indicates that salt retention promotes the secretion of endogenous ouabain (EO), an adrenocortical hormone...
  11. The Role of a Cerebello-Thalamo-Basal Ganglia Pathway in Dystonia
    Rachel Fremont; Fiscal Year: 2013
    ..In rodents, perfusing a selective Na/K ATPase (sodium pump) blocker ouabain into the cerebellum results in dystonia...
  12. Na,K-ATPase mediated ouabain effects in polycystic kidney disease
    V GUSTAVO BLANCO; Fiscal Year: 2013
    ..Interestingly, besides its activity as an ion transporter, the Na,K-ATPase also functions as the receptor for ouabain. Ouabain is a well characterized hormone known to trigger signaling events that induce changes in metabolism, ..
  13. Role of the Na, K-ATPase Alpha4 Isoform in Sperm Motility
    Paul James; Fiscal Year: 2009
    ..Specific pharmacological inhibition of this Na,K-ATPase isoform using the cardiac glycoside ouabain has been shown to completely inhibit the motility of rat sperm...
  14. AUTONOMIC CONTROL OF LACRIMAL GLAND FUNCTION
    BARRY BROMBERG; Fiscal Year: 1980
    ..Changes in lacrimal gland structure will be assessed by light microscopy and by autoradiography of 3H-ouabain binding to Na ion/K ion-ATPase...
  15. PATHOGENESIS OF HERPETIC KERATITIS
    WILLIAM O BRIEN; Fiscal Year: 2002
    ..upon endothelial cell function in vivo will be evaluated by measuring corneal thickness, endothelial cell number, ouabain binding, and barrier function...
  16. EFFECT OF VITAMIN E ON HEPATOCYTE STRUCTURE AND FUNCTION
    Ronald Sokol; Fiscal Year: 1991
    ..Taurocholate uptake, NaK-ATPase pump activity, ouabain uptake, and degree of lipid peroxidation will be determined in hepatocytes isolated from each experimental group ..
  17. AIRWAY PHARMACOLOGY DURING ONTOGENESIS
    James Douglas; Fiscal Year: 1993
    ..concentrations affect membrane receptors (histaminergic, cholinergic, adrenergic, 5-HT, leukotriene and ouabain) by changing their affinities, densities and/or coupling so that, subsequent to receptor activation, ..
  18. CELL NA IN VSM PROTEIN PRODUCTION
    JULIUS ALLEN; Fiscal Year: 1992
    ..and quantitate contractile protein content (actin and myosin) by gel electrophoresis, Na+ pump site number by H3-ouabain binding and Na+ pump turnover rate by ouabain sensitive Rb86 uptake...
  19. METABOLISM OF DIGITALIS LIKE FACTORS
    Roland Valdes; Fiscal Year: 2002
    ..DLIF may control the ion-transport activity of ouabain-sensitive sodium- potassium ATPase...
  20. NA PUMP--CHARACTERIZATION OF DIGITALIS BINDING SITE
    Kai Xu; Fiscal Year: 2001
    ..to achieve the objective: Aim 1, to identify the structural determinants at the digitalis binding pocket of both ouabain-sensitive (rabbit) and ouabain-resistant (rat) Na+, K+-ATPase, and to test the hypothesis that the newly ..
  21. TWO ISOFORMS OF NA,K-ATPASE IN THE HEART
    Yuk Chow Ng; Fiscal Year: 1992
    ..the high (alpha(alpha(+)) and the low (alpha) molecular with forms correspond to the high and low affinity ouabain binding sites, respectively...
  22. Shaping antibody Responses to Small Molecules by Design
    Behnaz Parhami Seren; Fiscal Year: 2006
    ..Our preliminary results using the plant-derived cadiotonic steroid-like digitalis glycoside, ouabain (Qua), indicate that the last 2 mechanisms are plausible and therefore we chose to test them...
  23. CHEMICAL STRUCTURE--HYPOTHALAMIC NA+/K+ ATPASE INHIBITOR
    GARNER HAUPERT; Fiscal Year: 1999
    ..analysis of pure HIF showed it to be an isomer, differing in the steroid moiety, of the plant glycoside, ouabain. Recently, an ouabain-like compound (OLC) isolated from human plasma and felt to be indistinguishable from plant ..
  24. BIOSYNTHESIS OF NOVEL ADRENOCORTICAL STEROIDS
    John Hamlyn; Fiscal Year: 2000
    ..Overwhelming structural and functional evidence shows the presence of an isomer of ouabain in the circulation, and tissues of mammals including man and cattle...
  25. DERIVATION OF REVERTANTS OF RAS-TRANSFORMED HUMAN CELLS
    LEONARD BENADE; Fiscal Year: 1992
    ..Following nitrosoguanidine mutation, flat revertants will be selected using ouabain treatment. KHOS is much more highly susceptible to ouabain than non- transformed, parental HOS cells...
  26. STUDIES OF RED CELL ION TRANSPORT AND LIPID BILAYERS
    ARTHUR SOLOMON; Fiscal Year: 1980
    ..mechanism responsible for the amplification affect by which a single molecule of the cation transport inhibitor, ouabain, affects the conformation 10 to 1000 copies of glycolytic enzymes coupled to the transport system...
  27. MOLECULAR BASIS OF CARDIAC GLYCOSIDE AFFINITY
    THOMAS PRESSLEY; Fiscal Year: 1992
    ..Na,K-ATPase) is thought to be the major pharmacological receptor for cardiac glycosides such as digitalis and ouabain. It is a membrane-spanning protein complex that mediates the transmembrane exchange of Na+ and K+ at the expense ..
  28. ALPHA ADRENERGIC REGULATION OF THE VASCULAR NA+ PUMP
    Stephen Navran; Fiscal Year: 1992
    ..under quiescent or proliferating conditions will be characterized with respect to Na+/K+ pump number by (3H) ouabain binding, turnover rate of the Na+/K+ pump by monitoring ouabain-sensitive 86Rb uptake, 22Na influx and numbers of ..
  29. CARCINOGEN TESTING: A MOUSE LYMPHOMA MUTATION SYSTEM
    Henry Bourne; Fiscal Year: 1980
    ..Mutants resistant to dibutyryl cyclic AMP, dexamethasone, 6-thioguanine or ouabain are well-suited for quantitative analysis of induction...
  30. STRUCTURE/FUNCTION STUDY OF NA+/K+ ATPASE
    Lois Lane; Fiscal Year: 1999
    ..3) to identify domains and residues that are involved directly and indirectly in the enzyme's interaction with ouabain and related drugs...
  31. ANALYSIS OF CARDIAC GLYCOSIDE AFFINITY IN CULTURED CELLS
    THOMAS PRESSLEY; Fiscal Year: 1993
    The Na, K-pump (ie., Na, K-ATPase) is thought to be the major pharmacological receptor for digitalis such as ouabain. It is an intrinsic membrane protein complex that extrudes Na+ from the cell and absorbs K+ from the exterior at the ..
  32. ROLE OF ION TRANSPORT RENAL CYST GROWTH
    William Macias; Fiscal Year: 1992
    ..the ion transport systems of cyst forming cells, activities will be measured in the presence of furosemide, ouabain, and amiloride...
  33. THE SITE AND MECHANISM OF PLASMA MEMBRANE RENEWAL
    Fred Hossler; Fiscal Year: 1980
    ..b>Ouabain binding, and 3H-ouabain autoradiography have been used to localize and quantitate the Na, K-ATPase (a primary ..
  34. IN VITRO INDUCTION & MODULATION OF MAMMARY PRENEOPLASIA
    Nitin Telang; Fiscal Year: 1991
    ..will be evaluated at the molecular level by measuring the induction of DNA damage/repair and 6-thioguanine and/or Ouabain resistant (TGr/OUr) mutants...
  35. MOLECULAR ANALYSIS OF NA+/K+-ATPASE
    Robert Levenson; Fiscal Year: 1992
    ..Initial experiments will involve the construction of chimeric cDNA molecules between cDNA molecules encoding ouabain resistant and ouabain sensitive forms of the Na,K-ATPase in order to delineate regions of the alpha chain which ..
  36. Calcium Signaling in Vasa Recta Endothelium
    THOMAS PALLONE; Fiscal Year: 2004
    ..We will test the hypothesis that high ouabain affinity Na+ pump isoforms modulate DVR endothelial Ca2+ signaling and participate in Angll signaling...
  37. REGULATION OF ION FLUXES BY THE INSULIN RECEPTOR
    Nicola Longo; Fiscal Year: 1999
    ..This will be determined by a combined approach involving measurement of insulin-induced changes in ouabain binding and biotin labeling of ion transporters on the plasma membrane of intact cells, Western blot analysis on ..
  38. NA,K-ATPASE REGULATION IN INTESTINE
    Michael Field; Fiscal Year: 1992
    ..Na and K affinities of intestinal Na, K-ATPase under control conditions, and under conditions which modify ouabain sensitivity (measurements will be made in both intact cells and isolated membranes); (2) purify rat intestinal Na,..
  39. STRUCTURE AND MECHANISM OF MEMBRANE TRANSPORT SYSTEMS
    CHARLES GRISHAM; Fiscal Year: 1990
    ..A new ouabain spin label prepared in this laboratory will be used to examine the ouabain binding site and the extracellular ..
  40. CADMIUM TOXICITY ANTAGONIZED BY DIFFERENTIATION-INDUCERS
    CHARLES SHOPSIS; Fiscal Year: 1990
    ..Na butyrate, hypoxanithine, hexamethylene bisacetamide, N-methyl formamide, N,N'-dimethyl formamide, hemin, ouabain and dimethyl acetamide, also have in common the capacity to induce differentiation in vitro in Friend ..
  41. EFFECTS OF BENZODIAZEPINES ON THICK ASCENDING LIMB
    Fuad Ziyadeh; Fiscal Year: 1992
    ..Furthermore, preliminary evidene suggests that BZD increases urinary sodium excretion, inhibit ouabain-sensitive oxygen consumption by medullary TALH and lower cytosolic calcium concentration...
  42. NA-K ATPASE ISOFORMS--FUNCTION AND LOCALIZATION
    Michael Tamkun; Fiscal Year: 1992
    ..Differences in ouabain sensitivity between the endogenous and expressed ATPase will allow pharmacological separation of mouse and ..
  43. PHYSIOLOGY OF ION TRANSPORT MECHANISM OF THE NA PUMP
    Bliss Forbush; Fiscal Year: 1992
    ..subunits of Na, K-ATPase, a low molecular weight membrane protein, a putative gamma subunit, is photolabeled by ouabain derivatives that are specifically bound to the enzyme...
  44. MOLECULAR STRUCTURE OF THE OUABAIN SENSITIVE ATPASE
    Jack Kyte; Fiscal Year: 1980
    ..As more and more information is gathered, it will be possible to coil the protein into a rough approximation of its three-dimensional structure...
  45. EFFECT OF AGING ON RENAL EPITHELIAL CELLS
    Patricia Wilson; Fiscal Year: 1991
    ..cells include electron microscopy, assessment of DNA synthesis (3H-thymidine uptake) and Na-K ATPase activity (3H-ouabain binding), histocytochemistry and determination of the effect of pertussis and cholera toxins and forskolin on ..
  46. MECHANISM OF CATION TRANSPORT REGULATION
    Lewis Cantley; Fiscal Year: 1993
    ..The study of the (Na,K)ATPase will focus on the mechanism by which expression of a novel "ouabain resistance gene" results in a totally ouabain insensitive (Na,K)ATPase in the plasma membrane of green monkey CV-..
  47. STRUCTURE-FUNCTION ANALYSIS OF NA/K-ATPASE ISOFORMS
    BRUCE KONE; Fiscal Year: 1993
    ..ion-sensitive electrode system will be used to characterize the ion transport parameters and sensitivity to ouabain for each of the major alpha- subunit isoforms expressed in mouse L cells...
  48. NA-K PUMP FUNCTION IN TRANSPORTING OCULAR TISSUES
    Dayle Geroski; Fiscal Year: 1991
    ..These studies will employ the specific binding of tritiated ouabain to endothelial Na/K ATPase to quantitate alterations in pump site density and distribution...
  49. MOLECULAR PHYSIOLOGY OF THE NA, K-ATPASE
    Robert Mercer; Fiscal Year: 1992
    ..The interaction of the cardiac glycoside, ouabain, with the Na,K-ATPase will be studied using the Na,K- ATPase from the ouabain-resistant rat...
  50. Neuroprotection in the Human Brain Tissue Model of Stroke
    SERGEI KIROV; Fiscal Year: 2009
    ..AD will be induced by oxygen-glucose deprivation, an in vitro ischemia model, or by application of ouabain, a sodium- potassium pump blocker...
  51. IONS, WATER, AND HYPERTENSION
    HENRY OVERBECK; Fiscal Year: 1980
    ..We will measure ouabain-sensitive Rb86 uptake, (H3)-ouabain binding, (V-P32)-ATPase binding, Na ion, K ion-ATPase activity and membrane ..
  52. CONTROL OF PAI-1 BY HEMORRHAGE
    Donald Gann; Fiscal Year: 2002
    ..has been found in apparent concentration to be sufficient to inhibit completely membrane Na/K ATPase (compared to ouabain)...
  53. Na+, Ca2+, Arterial Contractility and Ouabain Hypertension
    Mordecai Blaustein; Fiscal Year: 2009
    ..Salt retention as a result of excessive intake or reduced renal excretion, leads to elevation of the endogenous ouabain (EO) level in plasma...
  54. PHYSIOLOGICAL CONTROL OF MYOCARDIAL NA,K-PUMP EXPRESSION
    Faramarz Ismail Beigi; Fiscal Year: 1991
    ..and alpha2 polypeptide subunits moreover has been correlated respectively with the presence of low- and high-ouabain-affinity Na, K- pump sites...
  55. Total Synthesis of Ouabain, a Potent Cardiac Glycoside
    NEIL GARG; Fiscal Year: 2006
    ..b>Ouabain, an important member of this class, has found utility in modern medicine for the treatment of congestive heart ..
  56. MECHANISM OF INSULIN ACTION UPON SODIUM PUMP
    Richard Moore; Fiscal Year: 1980
    ..The stimulation of 22Na efflux by insulin into K-free Ringer containing ouabain will be investigated...
  57. ALTERATIONS OF TRANSPORT SYSTEMS IN HIV-INFECTED CELLS
    Robert Garry; Fiscal Year: 1991
    ..the activity of the Na+/K+ ATPase will be elucidated by kinetic analysis of 86Rb+ uptake and by binding of (3H) ouabain in intact cells...
  58. Proteomics of M-L antigens modulating cation transport
    PETER LAUF; Fiscal Year: 2004
    ....
  59. Third Symposium Cell Volume & Signalling Regulation
    PETER LAUF; Fiscal Year: 2003
    ..This meeting's success on U.S. soil will foster continuation of gathering of high-caliber scientists at subsequent international meetings ..
  60. Measurement of Fluid Flow Across the Ocular Ciliary Body
    OSCAR CANDIA; Fiscal Year: 2006
    ..abstract_text> ..
  61. SOLUTE AND FLUID TRANSPORT ACROSS THE CONJUNCTIVA
    OSCAR CANDIA; Fiscal Year: 2002
    ..Based on this model, he will devise protocols to modify and possibly reverse the secretory/absorptive properties of the tissue. ..
  62. Fluid Movement across Conjunctiva: Stimulation and Regulation
    OSCAR CANDIA; Fiscal Year: 2007
    ..These studies may provide the groundwork for the design of future treatment modalities for dry-eye syndromes. ..