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1

Fu, Yong, Dalian Ding, Lei Wei, Haiyan Jiang, and Richard Salvi. "Ouabain-Induced Apoptosis in Cochlear Hair Cells and Spiral Ganglion NeuronsIn Vitro." BioMed Research International 2013 (2013): 1–16. http://dx.doi.org/10.1155/2013/628064.

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Ouabain is a common tool to explore the pathophysiological changes in adult mammalian cochleain vivo. In prior studies, locally administering ouabain via round window membrane demonstrated that the ototoxic effects of ouabainin vivovaried among mammalian species. Little is known about the ototoxic effectsin vitro. Thus, we prepared cochlear organotypic cultures from postnatal day-3 rats and treated these cultures with ouabain at 50, 500, and 1000 μM for different time to elucidate the ototoxic effects of ouabainin vitroand to provide insights that could explain the comparative ototoxic effects
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2

Teixeira, Mariana Pires, Natalia Ferreira Haddad, Eliza Freitas Passos, et al. "Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells." Cancers 14, no. 24 (2022): 6168. http://dx.doi.org/10.3390/cancers14246168.

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Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients’ survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain’s effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability we
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3

Curras, M. C., and J. A. Boulant. "Effects of ouabain on neuronal thermosensitivity in hypothalamic tissue slices." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 257, no. 1 (1989): R21—R28. http://dx.doi.org/10.1152/ajpregu.1989.257.1.r21.

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To determine the role of the electrogenic Na+-K+ pump in neuronal thermosensitivity, single-unit activity was recorded in rat hypothalamic tissue slices before, during, and after perfusions containing 10(-5) or 10(-6) M ouabain, a specific pump inhibitor. Most neurons were recorded in the preoptic-anterior hypothalamus. Some neurons were also tested with high magnesium-low calcium perfusions to determine ouabain's effects on neuronal activity during synaptic blockade. When the neurons were characterized according to thermosensitivity, 24% were warm sensitive, 8% were cold sensitive, and 68% we
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4

Blanco, Gustavo, and Darren P. Wallace. "Novel role of ouabain as a cystogenic factor in autosomal dominant polycystic kidney disease." American Journal of Physiology-Renal Physiology 305, no. 6 (2013): F797—F812. http://dx.doi.org/10.1152/ajprenal.00248.2013.

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The classic role of the Na-K-ATPase is that of a primary active transporter that utilizes cell energy to establish and maintain transmembrane Na+ and K+ gradients to preserve cell osmotic stability, support cell excitability, and drive secondary active transport. Recent studies have revealed that Na-K-ATPase located within cholesterol-containing lipid rafts serves as a receptor for cardiotonic steroids, including ouabain. Traditionally, ouabain was viewed as a toxin produced only in plants, and it was used in relatively high concentrations to experimentally block the pumping action of the Na-K
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5

Lewis, Lynley K., Timothy G. Yandle, Philip J. Hilton, Berit P. Jensen, Evan J. Begg, and M. Gary Nicholls. "Endogenous Ouabain Is Not Ouabain." Hypertension 64, no. 4 (2014): 680–83. http://dx.doi.org/10.1161/hypertensionaha.114.03919.

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6

Sibarov, Dmitry A., Zoia D. Zhuravleva, Margarita A. Ilina, et al. "Unveiling the Role of Cholesterol in Subnanomolar Ouabain Rescue of Cortical Neurons from Calcium Overload Caused by Excitotoxic Insults." Cells 12, no. 15 (2023): 2011. http://dx.doi.org/10.3390/cells12152011.

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Na/K-ATPase maintains transmembrane ionic gradients and acts as a signal transducer when bound to endogenous cardiotonic steroids. At subnanomolar concentrations, ouabain induces neuroprotection against calcium overload and apoptosis of neurons during excitotoxic stress. Here, the role of lipid rafts in interactions between Na/K-ATPase, sodium–calcium exchanger (NCX), and N-methy-D-aspartate receptors (NMDARs) was investigated. We analyzed 0.5–1-nanometer ouabain’s effects on calcium responses and miniature post-synaptic current (mEPSCs) frequencies of cortical neurons during the action of NMD
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7

Gomez-Sanchez, Elise P., Mark F. Foecking, Deborah Sellers, Mary S. Blankenship, and Celso E. Gomez-Sanchez. "Is the Circulating Ouabain-like Compound Ouabain?" American Journal of Hypertension 7, no. 7_Pt_1 (1994): 637–46. http://dx.doi.org/10.1093/ajh/7.7.637.

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8

Gomez-Sanchez, Elise P., Mark F. Foecking, Sellers Deborah, Mary S. Blankenship, and Celso E. Gomez-Sanchez. "Is the Circulating Ouabain-like Compound Ouabain?" American Journal of Hypertension 7, no. 7_Pt_1 (1994): 647–50. http://dx.doi.org/10.1093/ajh/7.7.647.

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9

Grajpel, Barbara, Przemysław Grodzicki, and Leszek Janiszewski. "The effect of hypoxia and ouabain on the muscle resting potential of Periplaneta americana L." Acta Neurobiologiae Experimentalis 56, no. 1 (1996): 103–6. http://dx.doi.org/10.55782/ane-1996-1109.

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We have studied the effect of hypoxia and ouabain on the muscle resting potential (RP) of the cockroach Periplaneta americana L. The experiments were done in insects reared either in normoxic or hypoxic conditions and treated, or not treated, with ouabain. Hypoxic conditions decreased the RP by about. 11.6 mV. Ouabain decreased the RP by about 8.3 mV (ouabain 10(-5) mol/l) or 12.3 mV (ouabain 5 x 10(-5) mol/l). Hypoxia and ouabain decreased the RP by about 28.5 mV (ouabain 10(-5) mol/l) or 31.3 mV (ouabain 5 x 10(-5) mol/l).
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10

Kjeldsen, K. "Homogeneity of [3H]ouabain-binding sites in rat soleus muscle." Biochemical Journal 249, no. 2 (1988): 481–85. http://dx.doi.org/10.1042/bj2490481.

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Homogeneity or heterogeneity of rat soleus-muscle Na,K-ATPase (Na+ + K+-dependent ATPase) with respect to affinity for [3H]ouabain was evaluated. Since the standard method for measuring specific [3H]ouabain binding to rat skeletal-muscle samples includes subtraction of a value for non-specific [3H]ouabain uptake and retention, and a wash-out in the cold to remove [3H]ouabain from the extracellular phase, it was possible that these procedures could hide a class of [3H]ouabain-binding sites either with low affinity or with a rapid dissociation of [3H]ouabain. However, measurements of [3H]ouabain
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11

Parhami-Seren, Behnaz, Charles Bell, Michael N. Margolies, and Garner T. Haupert. "Monoclonal Antibodies That Distinguish Between Two Related Digitalis Glycosides, Ouabain and Digoxin." Journal of Immunology 163, no. 8 (1999): 4360–66. http://dx.doi.org/10.4049/jimmunol.163.8.4360.

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Abstract The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias. Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, but their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain. Our attempts to produce ouabain-specific mAbs were uns
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12

Dostanic, Iva, Richard J. Paul, John N. Lorenz, Steven Theriault, James W. Van Huysse та Jerry B. Lingrel. "The α2-isoform of Na-K-ATPase mediates ouabain-induced hypertension in mice and increased vascular contractility in vitro". American Journal of Physiology-Heart and Circulatory Physiology 288, № 2 (2005): H477—H485. http://dx.doi.org/10.1152/ajpheart.00083.2004.

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Although ouabain is known to induce hypertension, the mechanism of how this cardiac glycoside affects blood pressure is uncertain. The present study demonstrates that the α2-isoform of the Na-K-ATPase mediates the pressor effects of ouabain in mice. To accomplish this, we analyzed the effect of ouabain on blood pressure in wild-type mice, where the α2-isoform is sensitive to ouabain, and genetically engineered mice expressing a ouabain-insensitive α2-isoform of the Na-K-ATPase. Thus differences in the response to ouabain between these two genotypes can only be attributed to the α2-isoform of N
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13

Anwer, M. S. "Effects of ion substitution on transport and choleretic effect of ouabain." American Journal of Physiology-Gastrointestinal and Liver Physiology 252, no. 3 (1987): G357—G364. http://dx.doi.org/10.1152/ajpgi.1987.252.3.g357.

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The role of inorganic ions in hepatic transport and choleretic effect of ouabain was studied in isolated perfused rat liver to verify whether Na+-coupled ouabain uptake into hepatocytes is responsible for the choleretic effect. Hepatic uptake and clearance of ouabain were not significantly affected when perfusate Na+ was replaced by Li+ or choline+, chloride by nitrate or isethionate, or bicarbonate by tricine. However, these ion substitutions, with the exception of Li+, significantly reduced ouabain-induced choleresis and biliary electrolyte excretion. When ouabain was infused at different ra
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14

Khundmiri, Syed J., Melissa A. Metzler, Mohamed Ameen, Vishal Amin, Madhavi J. Rane, and Nicholas A. Delamere. "Ouabain induces cell proliferation through calcium-dependent phosphorylation of Akt (protein kinase B) in opossum kidney proximal tubule cells." American Journal of Physiology-Cell Physiology 291, no. 6 (2006): C1247—C1257. http://dx.doi.org/10.1152/ajpcell.00593.2005.

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Cardiotonic glycosides, like ouabain, inhibit Na+-K+-ATPase. Recent evidence suggests that low molar concentrations of ouabain alter cell growth. Studies were conducted to examine the effect of ouabain on Akt phosphorylation and rate of cell proliferation in opossum kidney (OK) proximal tubule cells. Cells exposed to 10 nM ouabain displayed increased Akt Ser473 phosphorylation, as evidenced by an increase in phospho-Akt Ser473 band density. Ouabain-stimulated Akt Ser473 phosphorylation was inhibited by pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitors (LY294002 and wortmannin),
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15

Raina, Hema, Qingli Zhang, Albert Y. Rhee, Thomas L. Pallone, and W. Gil Wier. "Sympathetic nerves and the endothelium influence the vasoconstrictor effect of low concentrations of ouabain in pressurized small arteries." American Journal of Physiology-Heart and Circulatory Physiology 298, no. 6 (2010): H2093—H2101. http://dx.doi.org/10.1152/ajpheart.01045.2009.

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We hypothesized that in salt-dependent forms of hypertension, endogenous ouabain acts on arterial smooth muscle to cause enhanced vasoconstriction. Here, we tested for the involvement of the arterial endothelium and perivascular sympathetic nerve terminals in ouabain-induced vasoconstriction. Segments of rat mesenteric or renal interlobar arteries were pressurized to 70 mmHg at 37°C and exposed to ouabain (10−11–10−7 M). Removal of the endothelium enhanced ouabain-induced vasoconstriction by as much as twofold (at an ouabain concentration of 10−9 M). A component of the ouabain-induced vasocons
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16

Emanuel, J. R., S. Graw, D. Housman, and R. Levenson. "Identification of a region within the Na,K-ATPase alpha subunit that contributes to differential ouabain sensitivity." Molecular and Cellular Biology 9, no. 9 (1989): 3744–49. http://dx.doi.org/10.1128/mcb.9.9.3744-3749.1989.

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To analyze determinants within the Na,K-ATPase alpha subunit that contribute to differential ouabain sensitivity, we constructed and expressed a panel of chimeric cDNA molecules between ouabain-resistant and ouabain-sensitive alpha subunit cDNAs. When introduced into ouabain-sensitive monkey CV-1 cells, ouabain-resistant rat alpha 1 subunit cDNA and chimeras in which the 5' end of ouabain-sensitive human alpha 1 or rat alpha 2 subunit cDNA was replaced by the 5' end of rat alpha 1 subunit cDNA conferred resistance to 100 microM ouabain. Monkey cells transfected with the reciprocal chimeras wer
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17

Emanuel, J. R., S. Graw, D. Housman, and R. Levenson. "Identification of a region within the Na,K-ATPase alpha subunit that contributes to differential ouabain sensitivity." Molecular and Cellular Biology 9, no. 9 (1989): 3744–49. http://dx.doi.org/10.1128/mcb.9.9.3744.

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To analyze determinants within the Na,K-ATPase alpha subunit that contribute to differential ouabain sensitivity, we constructed and expressed a panel of chimeric cDNA molecules between ouabain-resistant and ouabain-sensitive alpha subunit cDNAs. When introduced into ouabain-sensitive monkey CV-1 cells, ouabain-resistant rat alpha 1 subunit cDNA and chimeras in which the 5' end of ouabain-sensitive human alpha 1 or rat alpha 2 subunit cDNA was replaced by the 5' end of rat alpha 1 subunit cDNA conferred resistance to 100 microM ouabain. Monkey cells transfected with the reciprocal chimeras wer
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18

Bauer, N., G. Scheiner-Bobis, and W. Schoner. "„Endogenes Digitalis” – der lange Weg vom herzwirksamen pflanzlichen Toxin zum Hormon der Säuger." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 34, no. 06 (2006): 389–97. http://dx.doi.org/10.1055/s-0037-1622553.

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ZusammenfassungEndogene Herzglykoside wurden kürzlich aus Blut, Urin, Nebennieren und Hypothalamus von Säugetieren isoliert und in ihrer Struktur aufgeklärt. Zu den endogenen Herzglykosiden zählen so gut bekannte Hemmstoffe der Natriumpumpe wie Ouabain (g-Strophanthin), Digoxin und Marinobufagenin. Endogenes Ouabain und Digoxin werden in der Nebennierenrinde der Säuger aus Progesteron und Pregnenolon synthetisiert. Ouabain wird bei Kreislaufbelastung rasch freigesetzt, seine Konzentration fällt bei Ruhe innerhalb weniger Minuten wieder ab. ACEInhibitoren und β-Blocker verhindern bei Hunden die
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19

Vakkuri, Olli, Sighvatur S. Arnason, Päivi Joensuu, Jorma Jalonen, Olli Vuolteenaho, and Juhani Leppäluoto. "Radioiodinated Tyrosyl-Ouabain and Measurement of a Circulating Ouabain-like Compound." Clinical Chemistry 47, no. 1 (2001): 95–101. http://dx.doi.org/10.1093/clinchem/47.1.95.

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Abstract Background: Assays for endogenous ouabain, a cardiac glycoside believed to be involved in blood pressure and volume regulation, are characterized by laboratory-specific plasma values that are measured by different assays. Because of this variability, our study focused on the development of a new 125I-labeled ouabain derivative for RIA of high sensitivity. Methods: We generated rabbit antisera against a ouabain-thyroglobulin conjugate. A tyrosylated ouabain derivative for radioiodination was synthesized using periodate and sodium cyanoborohydride reagents. Results: Mass spectrometric a
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20

Cao, Chunhua, Kristie Payne, Whaseon Lee-Kwon, et al. "Chronic ouabain treatment induces vasa recta endothelial dysfunction in the rat." American Journal of Physiology-Renal Physiology 296, no. 1 (2009): F98—F106. http://dx.doi.org/10.1152/ajprenal.90429.2008.

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Descending vasa recta (DVR) are 15-μm vessels that perfuse the renal medulla. Ouabain has been shown to augment DVR endothelial cytoplasmic Ca2+ ([Ca2+]CYT) signaling. In this study, we examined the expression of the ouabain-sensitive Na-K-ATPase α2 subunit in the rat renal vasculature and tested effects of acute ouabain exposure and chronic ouabain treatment on DVR. Immunostaining with antibodies directed against the α2 subunit verified its expression in both DVR pericytes and endothelium. Acute application of ouabain (100 or 500 nM) augmented the DVR nitric oxide generation stimulated by ace
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Weiss, D. N., D. J. Podberesky, J. Heidrich, and M. P. Blaustein. "Nanomolar ouabain augments caffeine-evoked contractions in rat arteries." American Journal of Physiology-Cell Physiology 265, no. 5 (1993): C1443—C1448. http://dx.doi.org/10.1152/ajpcell.1993.265.5.c1443.

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Chronic parenteral administration of ouabain to normal rats raises plasma ouabain concentrations to low nanomolar levels and induces hypertension [C. M. Yuan, P. Manunta, J. M. Hamlyn, S. W. Chen, E. Bohen, J. Yeun, F. J. Haddy, and M. B. Pamnani. Hypertension 22: 178-187, 1993 and see also M. P. Blaustein. Am. J. Physiol. 264 (Cell Physiol. 33): C1367-C1387, 1993]. To determine whether rat arteries are sensitive to these low ouabain levels, we tested the effects of various ouabain concentrations on caffeine-evoked contractions (CEC) in rat aortic and small mesenteric artery rings. CEC amplitu
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22

Stimers, J. R., L. A. Lobaugh, S. Liu, N. Shigeto, and M. Lieberman. "Intracellular sodium affects ouabain interaction with the Na/K pump in cultured chick cardiac myocytes." Journal of General Physiology 95, no. 1 (1990): 77–95. http://dx.doi.org/10.1085/jgp.95.1.77.

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Whether a given dose of ouabain will produce inotropic or toxic effects depends on factors that affect the apparent affinity (K0.5) of the Na/K pump for ouabain. To accurately resolve these factors, especially the effect of intracellular Na concentration (Nai), we have applied three complementary techniques for measuring the K0.5 for ouabain in cultured embryonic chick cardiac myocytes. Under control conditions with 5.4 mM Ko, the value of the K0.5 for ouabain was 20.6 +/- 1.2, 12.3 +/- 1.7, and 6.6 +/- 0.4 microM, measured by voltage-clamp, Na-selective microelectrode, and equilibrium [3H]oua
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23

Boulanger, B. R., M. P. Lilly, J. M. Hamlyn, J. Laredo, D. Shurtleff, and D. S. Gann. "Ouabain is secreted by the adrenal gland in awake dogs." American Journal of Physiology-Endocrinology and Metabolism 264, no. 3 (1993): E413—E419. http://dx.doi.org/10.1152/ajpendo.1993.264.3.e413.

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Ouabain has been identified in the plasma and adrenal glands of several mammals, including humans. To investigate possible adrenal secretion of ouabain in vivo, at rest, and in response to acute blood volume changes, we prepared trained adult dogs (n = 10) with splenectomy and unilateral adrenal venous (AV) cannulation. Two days later, after an overnight fast, dogs had either 1) 20% hemorrhage (hem) or 2) 20% blood volume expansion (exp; 6% Dextran 70, 0.9% NaCl) in random order. In AV and arterial plasma (ART), ouabain was measured by a ouabain-specific immunoassay, and cortisol and aldostero
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Tamura, M., D. W. Piston, M. Tani, M. Naruse, E. J. Landon, and T. Inagami. "Ouabain increases aldosterone release from bovine adrenal glomerulosa cells: role of renin-angiotensin system." American Journal of Physiology-Endocrinology and Metabolism 270, no. 1 (1996): E27—E35. http://dx.doi.org/10.1152/ajpendo.1996.270.1.e27.

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To evaluate the potential physiological significance of ouabain or a ouabainlike substance, we investigated the effect of nanomolar concentrations of ouabain on aldosterone release by cultured bovine adrenal glomerulosa cells. Ouabain (10 nM) increased aldosterone release from 0.35 to 0.89 ng.mg-1.4 h-1 in the serum-containing medium. Losartan prevented this increase. When angiotensinogen was added to the nonserum medium, 10 nM ouabain enhanced the aldosterone release. Losartan again blocked the increase. These findings together with a stimulation of renin release by ouabain indicate that angi
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Brownlee, A. A., Paul Johnson, and Ivor H. Mills. "Actions of bufalin and cinobufotalin, two bufadienolides respectively more active and less active than ouabain, on ouabain binding and 86Rb uptake by human erythrocytes." Clinical Science 78, no. 2 (1990): 169–74. http://dx.doi.org/10.1042/cs0780169.

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1. We have reported that the bufadienolide, bufalin (purified from toad skin), was more potent than ouabain in inhibiting the sodium/potassium-dependent adenosine triphosphatase from canine kidney (Sigma) [Brownlee, A. A., Lee, G. & Mills, I. H. J. Physiol. (London) 1987; 390, 94P]. 2. The activities of bufalin and cinobufotalin were compared with ouabain in the [3H]ouabain binding assay and on 86Rb uptake in human erythrocytes. 3. When the percentage binding of ouabain-sensitive [3H]ouabain was plotted against the log of the concentration of drug in mol/l, it was shown that the bufalin cu
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Murrell, Julie R., Jeffrey D. Randall, James Rosoff, et al. "Endogenous Ouabain." Circulation 112, no. 9 (2005): 1301–8. http://dx.doi.org/10.1161/circulationaha.105.554071.

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Hamlyn, John M., and Mordecai P. Blaustein. "Endogenous Ouabain." Hypertension 68, no. 3 (2016): 526–32. http://dx.doi.org/10.1161/hypertensionaha.116.06599.

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Blaustein, Mordecai P., and John M. Hamlyn. "Ouabain, endogenous ouabain and ouabain-like factors: The Na+ pump/ouabain receptor, its linkage to NCX, and its myriad functions." Cell Calcium 86 (March 2020): 102159. http://dx.doi.org/10.1016/j.ceca.2020.102159.

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Zeng, Weian, Shuji Dohi, Hiroyuki Shimonaka, and Toshio Asano. "Spinal Antinociceptive Action of Na+-K+Pump Inhibitor Ouabain and Its Interaction with Morphine and Lidocaine in Rats." Anesthesiology 90, no. 2 (1999): 500–508. http://dx.doi.org/10.1097/00000542-199902000-00026.

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Background The Na+,K+-adenosine triphosphatase is a ubiquitous enzyme system that maintains the ion gradient across the plasma membrane of a variety of cell types, including cells in the central nervous system. We investigated the antinociceptive effect of intrathecally administered ouabain and examined its potential interaction with spinal morphine and lidocaine. Methods Using rats chronically implanted with lumbar intrathecal catheters, the ability of intrathecally administered ouabain, morphine, and lidocaine and of mixtures of ouabain-morphine and ouabain-lidocaine to alter tail-flick late
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Mandal, Amritlal, Nicholas A. Delamere, and Mohammad Shahidullah. "Ouabain-induced stimulation of sodium-hydrogen exchange in rat optic nerve astrocytes." American Journal of Physiology-Cell Physiology 295, no. 1 (2008): C100—C110. http://dx.doi.org/10.1152/ajpcell.90636.2007.

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Sodium-dependent transporters are inhibited indirectly by the Na-K-ATPase inhibitor ouabain. Here we report stimulation of sodium-hydrogen exchange (NHE) in ouabain-treated cells. BCECF was used to measure cytoplasmic pH in cultured rat optic nerve astrocytes. Ammonium chloride was applied to acid load the cells. On removal of ammonium chloride, cytoplasmic pH fell abruptly, then gradually recovered toward baseline. Ouabain (1 μM) did not change cell sodium content, but the rate of pH recovery increased by 68%. Ouabain speeded pH recovery both in the presence and absence of bicarbonate. In bic
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Nesher, Maoz, Yan Bai, Daxiang Li, Haim Rosen, David Lichtstein, and Lijun Liu. "Interaction of atrial natriuretic peptide and ouabain in the myocardium." Canadian Journal of Physiology and Pharmacology 90, no. 10 (2012): 1386–93. http://dx.doi.org/10.1139/y2012-112.

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Natriuretic peptides and digitalis-like compounds serve as regulators of homeostasis, including control of volume expansion and blood pressure. The aim of the present study was to explore possible interactions between atrial natriuretic peptide (ANP) and ouabain in the heart. ANP (1 nmol/L) had no effect in papillary muscle preparations from guinea pigs. Ouabain (1 µmol/L) induced positive inotropic effect. The addition of ANP prior to ouabain resulted in a significant decrease in the ouabain-induced positive inotropic effect, manifested as an attenuated increase in twitch maximal upward force
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McLaughlin, Charles W., Sylvia Zellhuber-McMillan, Anthony D. C. Macknight, and Mortimer M. Civan. "Electron microprobe analysis of rabbit ciliary epithelium indicates enhanced secretion posteriorly and enhanced absorption anteriorly." American Journal of Physiology-Cell Physiology 293, no. 5 (2007): C1455—C1466. http://dx.doi.org/10.1152/ajpcell.00205.2007.

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The rate of aqueous humor formation sequentially across the pigmented (PE) and nonpigmented (NPE) ciliary epithelial cell layers may not be uniform over the epithelial surface. Because of the tissue's small size and complex geometry, this possibility cannot be readily tested by conventional techniques. Rabbit iris-ciliary bodies were divided, incubated, quick-frozen, cryosectioned, and freeze-dried for electron probe X-ray microanalysis of the elemental contents of the PE and NPE cells. We confirmed that preincubation with ouabain to block Na+,K+-ATPase increases Na+ and decreases K+ contents
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Nascimento, C. R., R. C. Valente, J. Echevarria-Lima, et al. "The Influence of Ouabain on Human Dendritic Cells Maturation." Mediators of Inflammation 2014 (2014): 1–15. http://dx.doi.org/10.1155/2014/494956.

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Although known as a Na,K-ATPase inhibitor, several other cellular and systemic actions have been ascribed to the steroid Ouabain (Oua). Particularly in the immune system, our group showed that Ouabain acts on decreasing lymphocyte proliferation, synergizing with glucocorticoids in spontaneous thymocyte apoptosis, and also lessening CD14 expression and blocking CD16 upregulation on human monocytes. However, Ouabain effects on dendritic cells (DCs) were not explored so far. Considering the peculiar plasticity and the importance of DCs in immune responses, the aim of our study was to investigate
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Shao, Chao, Shengwei Lin, Sudan Liu та ін. "HIF1α-Induced Glycolysis in Macrophage Is Essential for the Protective Effect of Ouabain during Endotoxemia". Oxidative Medicine and Cellular Longevity 2019 (28 квітня 2019): 1–10. http://dx.doi.org/10.1155/2019/7136585.

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Ouabain, a steroid binding to the Na+/K+-ATPase, has several pharmacological effects. In addition to the recognized effects of blood pressure, there is more convincing evidence suggesting that ouabain is involved in immunologic functions and inflammation. Hypoxia-inducible factor 1α (HIF-1α) is a metabolic regulator which plays a considerable role in immune responses. Previous studies had shown that HIF-1α-induced glycolysis results in functional reshaping in macrophages. In this study, we investigated the role of glycolytic pathway activation in the anti-inflammatory effect of ouabain. We fou
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de Vasconcelos, Danielle Ingrid Bezerra, Jacqueline Alves Leite, Luciana Teles Carneiro, et al. "Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice." Mediators of Inflammation 2011 (2011): 1–11. http://dx.doi.org/10.1155/2011/912925.

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Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory p
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36

Nguyen, Anh-Nguyet T., Kyle Jansson, Gladis Sánchez, et al. "Ouabain activates the Na-K-ATPase signalosome to induce autosomal dominant polycystic kidney disease cell proliferation." American Journal of Physiology-Renal Physiology 301, no. 4 (2011): F897—F906. http://dx.doi.org/10.1152/ajprenal.00095.2011.

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The Na-K-ATPase is part of a cell signaling complex, the Na-K-ATPase signalosome, which upon activation by the hormone ouabain regulates the function of different cell types. We previously showed that ouabain induces proliferation of epithelial cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD cells). Here, we investigated the signaling pathways responsible for mediating the effects of ouabain in these cells. Incubation of ADPKD cells with ouabain, in concentrations similar to those found in blood, stimulated phosphorylation of the epidermal gr
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Rajendran, Vazhaikkurichi M., Satish K. Singh, John Geibel, and Henry J. Binder. "Differential localization of colonic H+-K+-ATPase isoforms in surface and crypt cells." American Journal of Physiology-Gastrointestinal and Liver Physiology 274, no. 2 (1998): G424—G429. http://dx.doi.org/10.1152/ajpgi.1998.274.2.g424.

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Two distinct colonic H+-K+-adenosinetriphosphatase (H+-K+-ATPase) isoforms can be identified in part on the basis of their sensitivity to ouabain. The colonic H+-K+-ATPase α-subunit (HKcα) was recently cloned, and its message and protein are present in surface (and the upper 20% of crypt) cells in the rat distal colon. These studies were performed to establish the spatial distribution of the ouabain-sensitive and ouabain-insensitive components of both H+-K+-ATPase activity in apical membranes prepared from surface and crypt cells and K+-dependent intracellular pH (pHi) recovery from an acid lo
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Teixeira, Mariana Pires, and Vivian Mary Rumjanek. "Ouabain Affects the Expression of Activation Markers, Cytokine Production, and Endocytosis of Human Monocytes." Mediators of Inflammation 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/760368.

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Ouabain is a steroid capable of binding to and inhibiting Na+,-K+-ATPase. Studies have demonstrated some actions of ouabain on immune cells, which indicated both pro- and anti-inflammatory properties of this molecule. Nevertheless, its effects on human monocytes are still poorly understood. Thus, the present work investigated effects of ouabain in the activation and function of human adherent monocytes. Our results show that there is an increase in intracellular calcium levels already 5 minutes following monocyte treatment with 10−7 M of ouabain. Furthermore, monocytes expressed increased amou
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Cai, Haiping, Liang Wu, Weikai Qu, et al. "Regulation of apical NHE3 trafficking by ouabain-induced activation of the basolateral Na+-K+-ATPase receptor complex." American Journal of Physiology-Cell Physiology 294, no. 2 (2008): C555—C563. http://dx.doi.org/10.1152/ajpcell.00475.2007.

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The long-term effects of ouabain on transepithelial Na+ transport involve transcriptional downregulation of apical Na+/H+ exchanger isoform 3 (NHE3). The aim of this study was to determine whether ouabain could acutely regulate NHE3 via a posttranscriptional mechanism in LLC-PK1 cells. We observed that the basolateral, but not apical, application of ouabain for 1 h significantly reduced transepithelial Na+ transport. This effect was not due to changes in the integrity of tight junctions or increases in the intracellular Na+ concentration. Ouabain regulated the trafficking of NHE3 and subsequen
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Oh, V. M. S., E. A. Taylor, J. L. Ding, N. A. Boon, J. K. Aronson, and D. G. Grahame-Smith. "Enhancement of specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes by a dialysable factor in human and fetal calf serum." Clinical Science 72, no. 1 (1987): 71–79. http://dx.doi.org/10.1042/cs0720071.

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1. We have measured specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes incubated for up to 7 days in media containing different concentrations of fetal calf serum and human serum. 2. Incubation for periods of up to 7 days with fetal calf serum and human serum produced increases in both specific [3H]ouabain binding and ouabain sensitive 86rubidium influx that were dependent on concentration and time. 3. Neither specific [3H]ouabain binding nor ouabain sensitive 86rubidium influx was altered when dialysed serum was used, suggesting that both fetal ca
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Vakkuri, O., SS Arnason, A. Pouta, O. Vuolteenaho, and J. Leppaluoto. "Radioimmunoassay of plasma ouabain in healthy and pregnant individuals." Journal of Endocrinology 165, no. 3 (2000): 669–77. http://dx.doi.org/10.1677/joe.0.1650669.

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Ouabain was recently isolated from human plasma, bovine hypothalamus and bovine adrenal in attempts to identify endogenous substances inhibiting the cell membrane sodium pump. A number of radioimmunoassays have been developed in order to study the clinical significance of ouabain. The results have been controversial with regard to the presence and chemical nature of plasma ouabain-like immunoreactivity. We have now measured ouabain in healthy and pregnant individuals using solid-phase extraction of plasma samples followed by a new radioimmunoassay with the extraordinary sensitivity of at least
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Pasdois, Philippe, Casey L. Quinlan, Abraham Rissa, et al. "Ouabain protects rat hearts against ischemia-reperfusion injury via pathway involving src kinase, mitoKATP, and ROS." American Journal of Physiology-Heart and Circulatory Physiology 292, no. 3 (2007): H1470—H1478. http://dx.doi.org/10.1152/ajpheart.00877.2006.

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We showed recently that mitochondrial ATP-dependent K+ channel (mitoKATP) opening is required for the inotropic response to ouabain. Because mitoKATP opening is also required for most forms of cardioprotection, we investigated whether exposure to ouabain was cardioprotective. We also began to map the signaling pathways linking ouabain binding to Na+-K+-ATPase with the opening of mitoKATP. In Langendorff-perfused rat hearts, 10–80 μM ouabain given before the onset of ischemia resulted in cardioprotection against ischemia-reperfusion injury, as documented by an improved recovery of contractile f
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Zhang, Lin, Christian Aalkjaer, and Vladimir Matchkov. "The Na,K-ATPase-Dependent Src Kinase Signaling Changes with Mesenteric Artery Diameter." International Journal of Molecular Sciences 19, no. 9 (2018): 2489. http://dx.doi.org/10.3390/ijms19092489.

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Inhibition of the Na,K-ATPase by ouabain potentiates vascular tone and agonist-induced contraction. These effects of ouabain varies between different reports. In this study, we assessed whether the pro-contractile effect of ouabain changes with arterial diameter and the molecular mechanism behind it. Rat mesenteric small arteries of different diameters (150–350 µm) were studied for noradrenaline-induced changes of isometric force and intracellular Ca2+ in smooth muscle cells. These functional changes were correlated to total Src kinase and Src phosphorylation assessed immunohistochemically. Hi
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Shin, Hye Kyoung, Byung Jun Ryu, Sik-Won Choi, Seong Hwan Kim, and Kyunglim Lee. "Inactivation of Src-to-Ezrin Pathway: A Possible Mechanism in the Ouabain-Mediated Inhibition of A549 Cell Migration." BioMed Research International 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/537136.

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Ouabain, a cardiac glycoside found in plants, is primarily used in the treatment of congestive heart failure and arrhythmia because of its ability to inhibit Na+/K+-ATPase pump. Recently ouabain has been shown to exert anticancer effects but the underlying mechanism is not clear. Here, we explored the molecular mechanism by which ouabain exerts anticancer effects in human lung adenocarcinoma. Employing proteomic techniques, we found 7 proteins downregulated by ouabain in A549 including p-ezrin, a protein associated with pulmonary cancer metastasis in a dose-dependent manner. In addition, when
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45

Cunningham, M. J., C. S. Apstein, E. O. Weinberg, and B. H. Lorell. "Deleterious effect of ouabain on myocardial function during hypoxia." American Journal of Physiology-Heart and Circulatory Physiology 256, no. 3 (1989): H681—H687. http://dx.doi.org/10.1152/ajpheart.1989.256.3.h681.

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The effect of cardiac glycosides on myocardial function during hypoxia is controversial. Accordingly, we studied left ventricular performance during hypoxia and reoxygenation in the presence of a mildly inotropic, nontoxic dose of ouabain using isolated, isovolumic, buffer-perfused rabbit hearts. After 15 min of hypoxia, left ventricular developed pressure was less in the ouabain-treated group than in controls (35 +/- 4 vs. 55 +/- 3 mmHg, P less than 0.025). Left ventricular end-diastolic pressure (LVEDP) increased more during hypoxia in the presence of ouabain (9 +/- 1 to 32 +/- 7 with ouabai
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46

Pierre, Sandrine V., Yoann Sottejeau, Jean-Michel Gourbeau, Gladis Sánchez, Amjad Shidyak, and Gustavo Blanco. "Isoform specificity of Na-K-ATPase-mediated ouabain signaling." American Journal of Physiology-Renal Physiology 294, no. 4 (2008): F859—F866. http://dx.doi.org/10.1152/ajprenal.00089.2007.

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The ion transporter Na-K-ATPase functions as a cell signal transducer that mediates ouabain-induced activation of protein kinases, such as ERK. While Na-K-ATPase composed of the α1-polypeptide is involved in cell signaling, the role of other α-isoforms (α2, α3, and α4) in transmitting ouabain effects is unknown. We have explored this using baculovirus-directed expression of Na-K-ATPase polypeptides in insect cells and ERK phosphorylation as an indicator of ouabain-induced signaling. Ouabain addition to Sf-9 cells coexpressing Na-K-ATPase α1- and β1-isoforms stimulated ERK phosphorylation. In c
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Akimova, Olga A., James Van Huysse, Johanne Tremblay та Sergei N. Orlov. "Low efficiency of functional translation of ouabain-resistant α2-Na+,K+-ATPase mRNA in C7-MDCK epithelial cells". Canadian Journal of Physiology and Pharmacology 90, № 1 (2012): 83–88. http://dx.doi.org/10.1139/y11-113.

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Na+,K+-ATPase is a heterodimer consisting of catalytic α1–α4 and regulatory β1–β3 subunits. Recently, we reported that transfection with ouabain-resistant α1R-Na+,K+-ATPase rescues renal epithelial C7-MDCK cells exclusively expressing the ouabain-sensitive α1S-isoform from the cytotoxic action of ouabain. To explore the role of α2 subunit in ion transport and cytotoxic action of ouabain, we compared the effect of ouabain on K+ (86Rb) influx and the survival of ouabain-treated C7-MDCK cells stably transfected with α1R- and α2R-Na+,K+-ATPase. α2R mRNA in transfected cells was ∼8-fold more abunda
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48

Bai, Yan, Jian Wu, Daxiang Li, et al. "Differential roles of caveolin-1 in ouabain-induced Na+/K+-ATPase cardiac signaling and contractility." Physiological Genomics 48, no. 10 (2016): 739–48. http://dx.doi.org/10.1152/physiolgenomics.00042.2016.

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Binding of ouabain to cardiac Na+/K+-ATPase initiates cell signaling and causes contractility in cardiomyocytes. It is widely accepted that caveolins, structural proteins of caveolae, have been implicated in signal transduction. It is known that caveolae play a role in Na+/K+-ATPase functions. Regulation of caveolin-1 in ouabain-mediated cardiac signaling and contractility has never been reported. The aim of this study is to compare ouabain-induced cardiac signaling and contractility in wild-type (WT) and caveolin-1 knockout (cav-1 KO) mice. In contrast with WT cardiomyocytes, ouabain-induced
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49

Khundmiri, Syed J., Vishal Amin, Jeff Henson, et al. "Ouabain stimulates protein kinase B (Akt) phosphorylation in opossum kidney proximal tubule cells through an ERK-dependent pathway." American Journal of Physiology-Cell Physiology 293, no. 3 (2007): C1171—C1180. http://dx.doi.org/10.1152/ajpcell.00535.2006.

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Endogenous cardiotonic glycosides bind to the inhibitory binding site of the plasma membrane sodium pump (Na+/K+-ATPase). Plasma levels of endogenous cardiotonic glycosides increase in several disease states, such as essential hypertension and uremia. Low concentrations of ouabain, which do not inhibit Na+/K+-ATPase, induce cell proliferation. The mechanisms of ouabain-mediated response remain unclear. Recently, we demonstrated that in opossum kidney (OK) proximal tubular cells, low concentrations of ouabain induce cell proliferation through phosphorylation of protein kinase B (Akt) in a calci
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50

Maddrell, S. H., and J. A. Overton. "Stimulation of sodium transport and fluid secretion by ouabain in an insect malpighian tubule." Journal of Experimental Biology 137, no. 1 (1988): 265–76. http://dx.doi.org/10.1242/jeb.137.1.265.

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Ouabain, at all concentrations higher than 2 × 10(−7) mol l-1, stimulates the rate at which the Malpighian tubules of the insect, Rhodnius, transport sodium ions and fluid into the lumen. An effect on paracellular movement of sodium ions is unlikely because ouabain makes the electrical potential of the lumen more positive, which would slow diffusion of sodium into the lumen. Radioactive ouabain binds to the haemolymph-facing sides of the tubule cells but not to the luminal face. This binding is reduced in the presence of elevated levels of potassium or of non-radioactive ouabain. Bound ouabain
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