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Simon Breitenbach, Frank Lehmann-Horn, Karin Jurkat-Rott
Eplerenone, an aldosterone antagonist, repolarizes muscle membrane in-vitro and increases strength in-vivo in channelopathies. In Duchenne dystrophy, it is administered for cardiomyopathy. We studied its mechanism of action on skeletal muscle to test its suitability for increasing strength in Duchenne dystrophy. Using membrane potential measurements, quantitative PCR, ELISA, and Western blots, we examined the effects of eplerenone on skeletal muscle Na,K-ATPase. The repolarizing effect of eplerenone in muscle fibres was counteracted by oubain, an ATPase blocker...
October 2016: Acta Myologica: Myopathies and Cardiomyopathies: Official Journal of the Mediterranean Society of Myology
Alastair M Mathewson, William R Dunn
The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo-oxygenase inhibitors). The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined...
2014: PloS One
(no author information available yet)
Activity of Na,K-ATPase (Na+,K+-adenosine triphosphatase, EC in the whole erythrocytes was studied in dynamics of the complete rat alimentary starvation for 1, 3, 5, 7-8, and 10-12 days with water drinking ad libitum. There has been established a change of the erythrocyte Na,K-ATPase activity depending on the phase of starvation (the period connected with a certain level of metabolism). After the state on an empty stomach and adaptation to endogenous nutrition (the 0-I phase), from the 3rd to the 7-8th starvation day, the II phase, the period of compensated adaptation occurs (the euglycemia is preserved, the plateau level is preserved, the plateau level is achieved for protein loss and hormonal stimulation)...
March 2013: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
John W Funder
Two clinical trials will be reviewed, RALES(1) and ILLUMINATE.(2) In RALES, low-dose spironolactone in addition to standard of care, produced a 30% improvement in survival in progressive heart failure, commonly assumed to reflect deleterious effects of aldosterone, with spironolactone competing with aldosterone for cardiac mineralocorticoid receptors. Recent evidence, however, points to cortisol rather than aldosterone as the hormone activating cardiac mineralocorticoid receptors, under conditions of tissue damage, and spironolactone as acting by mechanisms other than receptor blockade...
September 2010: Hypertension Research: Official Journal of the Japanese Society of Hypertension
A O Sherstobitov, A V Lapin, V V Glazunov, A A Nikiforov
Mechanisms of transport of monovalent thallium across the membrane of oocyte of the lamprey Lampetra fluviatilis were studied by using 204Tl. Transport of Tl+ in lamprey oocytes has been shown to be realized by at least two pathways: through Na/K-pump and by the mechanism of Na,K,Cl-cotransport. In the standard Ringer solution (mM): 4 KCl, 140 NaCl, 0.5 CaCl2, 5 glucose, 10 Tris-HCl--in the presence of oubain, the coefficient of the 204Tl stationary distribution (cell/medium) was within the range of 2.3-2.5, while the time necessary to reach its 50 % value amounted to 40-5 min at 20 degrees C...
May 2010: Zhurnal Evoliutsionnoĭ Biokhimii i Fiziologii
I Hájek, J Teisinger
The inhibition by ouabain of Na(+), K(+) ATPase activity in lumbar spinal cord membranes followed a sigmoid curve and in sciatic nerve membranes an exponential curve. The degree of inhibition in spinal cord depended on the presence of opioid ligands; fractions became more sensitive to ouabain after removal of bound opioids. The saturation of receptors by specific ligands reversed the effect of preincubation. Opioids had no effect on Na(+), K(+) ATPase in sciatic nerve. Membranes isolated from spinal cord were highly sensitive to oubain inhibition and their Na(+), K(+) ATPase resembled that containing the ? (+) subunit; membranes from peripheral nerve were less sensitive to ouabain and their enzyme reacted as that containing the ? subunit...
1990: Neurochemistry International
Peter Kolkhof, Andreas Geerts, Stefan Schäfer, Jan Torzewski
Elevated plasma levels of C-reactive protein (CRP), the prototype acute-phase protein (APP), are predictive for future cardiovascular events. Controversial evidence suggests that CRP may play a causal role in cardiovascular disease. CRP synthesis inhibition is a potential approach for reducing cardiovascular mortality. We show here that endogenous and plant-derived inhibitors of the Na(+)/K(+)-ATPase, i.e. the cardiac glycosides ouabain and digitoxin, inhibit IL-1beta- and IL-6-induced APP expression in human hepatoma cells and primary human hepatocytes (PHH) at nanomolar concentrations...
March 26, 2010: Biochemical and Biophysical Research Communications
Larissa D Newton, Sulochana Krishnakumar, Ajitkumar Gopinadha Menon, John P Kastelic, Frans A van der Hoorn, Jacob C Thundathil
Incubation of bovine sperm with ouabain, an endogenous cardiac glycoside that inhibits both the ubiquitous (ATP1A1) and testis-specific alpha4 (ATP1A4) isoforms of Na(+)/K(+)ATPase, induces tyrosine phosphorylation and capacitation. The objectives of this study were to investigate: (1) fertilizing ability of bovine sperm capacitated by incubating with ouabain; (2) involvement of ATP1A4 in this process; and (3) signaling mechanisms involved in the regulation of sperm capacitation induced by inhibition of Na(+)/K(+)ATPase activity...
February 2010: Molecular Reproduction and Development
Xinggang Dong, Jianghua Chen, Qiang He, Yi Yang, Wei Zhang
To explore a new way of constructing bioartificial renal tubule assist device (RAD) in vitro and its function of transporting sodium (Na(+)) and glucose and to evaluate the application of atomic force microscope in the RAD construction, rat renal tubular epithelial cell line NRK-52E was cultured in vitro, seeded onto the outer surfaces of hollow fibers in a bioreactor, and then cultured for two weeks to construct RAD. Bioreactor hollow fibers without NRK-52E cells were used as control. The morphologies of attached cells were observed with scanning electron microscope, and the junctions of cells and polysulfone membrane were observed with atomic force microscope...
August 2009: Journal of Huazhong University of Science and Technology. Medical Sciences
Chiara Riganti, Ivana Campia, Manuela Polimeni, Gianpiero Pescarmona, Dario Ghigo, Amalia Bosia
Digoxin and ouabain are cardioactive glycosides, which inhibit the Na+/K+-ATPase pump and in this way they increase the intracellular concentration of cytosolic calcium ([Ca2+](i)). They are also strong inducers of the P-glycoprotein (Pgp), a transmembrane transporter which extrudes several drugs, including anticancer agents like doxorubicin. An increased amount of Pgp limits the absorption of drugs through epithelial cells, thus inducing resistance to chemotherapy. The mechanism by which cardioactive glycosides increase Pgp is not known and in this work we investigated whether digoxin and ouabain elicited the expression of Pgp with a calcium-driven mechanism...
November 1, 2009: Toxicology and Applied Pharmacology
A V Kipenko, V A Penniiaĭnen, E V Lopatina, I V Rogachevskiĭ, V A Tsyrlin, B V Krylov
Using the method of organotypical cell culture, experimental data was obtained supporting the hypothesis that chelate complex ouabain-Ca2+ modulates the transducer function of Na+, K+- ATPase. Quantum-chemical calculations helped to elucidate two principally distinct modes for chelation of Ca2+ ions by ouabain molecule. It is predicted that ligang-receptor complex of ouabain-Ca2+--Na+,K+-ATPase is formed due to ion-ionic bonds. The forming of this complex switches on the transducer function of the sodium pump...
February 2009: Rossiĭskii Fiziologicheskiĭ Zhurnal Imeni I.M. Sechenova
Ke-qian Zhi, Wen-hao Ren, Yu-ming Wen, Qun-ai Miao, Hong Li
OBJECTIVE: To study the mechanism of sensitivity variation to cisplatin caused by nm23-H1. METHODS: The samles was divided into two groups: Tca8113 group and Tca8113/nm23-H1 group. Using MTT and flow cytometer, the changes of cell mortality rate, apoptosis and mitochondrial membrane potential were detected. By VG PQ Excell, the changes of the intracellular platinum were detected. RESULTS: In vitro the cell mortality rate and apoptosis were increased in Tca8113/nm23-H1 group, comparing with Tea8113 group...
October 2008: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
I S Chekman
Leterature data and own investigations are summarized in the article. New experimental facts about mechanism of action of cardiac glycosides (especially digoxin) were obtained last year. It was shown that in human organism there are endogenous cardiosteroids (digitalis-like substances, endogenous oubain and other). They are in different organs (adrenal glands, hypothalamus, pituitary gland) and have influence on different organs and systems. Indications, contraindications, side effects, interactions with other drugs have been studied by cardiologists...
January 2008: Likars'ka Sprava
I A Karitskaia, N D Aksenov, I O Vasil'eva, E G Strelkova, I I Marakhova
In interleukin-2 (IL-2)-induced human blood lymphocytes, the Na+/K+ pump function (assessed by ouabain-sensitive Rb+ influx), the abundance of Na+, K+-ATPase alpha1-subunit (determined by Western blotting) and the alpha1- and beta1-subunits mRNA of Na+, K+-ATPase (RT-PCR), as well as the phosphorylation of STAT5 and STAT3 family proteins and ERK1/2 kinase have been examined. A 3.5-4.0-fold increase in the expression of alpha1- and beta1-subunits mRNA of Na+, K+-ATPase was found at 24 h of IL-2 stimulation. The inhibitors of JAK3 kinase (B-42, WHI-P431) was shown to decrease both the phosphorylation of STATs and the rise in the oubain-sensitive rubidium influx as well as the increased abundance of Na+, K+-ATPase alpha1-subunit...
2008: Tsitologiia
Sławomir Tubek
The total and ouabain-dependent rate constants of efflux of zinc (Zn) ions from lymphocytes isolated from healthy subjects were measured in vitro in an environment containing calcium (Ca) and magnesium (Mg) ions. Both the total (ERCt-Zn) and ouabain-dependent (ERCos-Zn) rate constants were higher in the presence of Mg2+, with the the oubain-dependent efflux significantly different 0.29+/-0.07 vs 0.13+/-0.02 with and without Mg2+, respectively (p<0.001). After the addition of verapamil, an increase of ERCE-Zn was observed in both ionic environments and was higher and statistically significant in the presence of Mg2+: 1...
2007: Biological Trace Element Research
Slawomir Tubek
The aim of this study was to compare zinc (Zn) metabolism parameters in groups of premenopausal and postmenopausal women with moderate and severe primary arterial hypertension. The study included 38 women, of which 15 were premenopausal and 23 were postmenopausal. Postmenopausal women had a positive correlation between total (ERCt- Zn) and oubain-dependent (ERCos-Zn) rate constants of Zn efflux from lymphocyte (k = 0.52). In premenopausal women's ERCos-Zn was negatively but weakly correlated with serum Zn (Zn-s) (k = 0...
June 2007: Biological Trace Element Research
Gaetano L Aiello, Enrico Bignetti, Carlo Casarino, Ivan D Sciacca, Michelangelo Scopelliti, Maurizio Venezia
Does a persistent blockage of the ionic pumps bring cell membrane voltage to zero? This apparently trivial question of basic cellular Biology stirred up an intriguing problem of nonlinear dynamics. A 3-ion model based on continuity and charge conservation proves that membrane voltage actually sets on a negative value, meaning that chemical equilibrium is never reached, rather an inversion of the Na+ concentration gradient occurs, usually hours after the blockage of the pumps. Experimental tests carried out with PC12 cells incubated with Oubaine for a period of 24 hours show an increase of cytosolic Na+ of about 266 mM/l with respect to a control sample...
July 2007: Nonlinear Dynamics, Psychology, and Life Sciences
T O Veklich, S O Kosterin, R V Rodik, S O Cherenok, V I Boĭko, V I Kal'chenko
Effect of calix[4]arenes C-97, C-99, C-107, functionalized by fragments of alpha-hydroxy-phosphonic, alpha-aminophosphonic- and methylene-bisphosphonic acid on enzymatic activity of oubaine-sensitive Na+, K+-ATPase and oubaine-resistant basal Mg2+- ATPase (specific activity - 10.6 +/- 0.9 and 18.1 +/- 1.2 micromol Pi/h per 1 mg of protein, respectively; n = 7) was studied in experiments made on the suspension of myometrium cell plasma membranes treated by 0.1% solution of digitonin. It was found that calixarene-phosphonic acids in concentration of 100 microM inhibited enzymatic activity of Na+, K+-ATPase by 86-98% and did not practically affect activity of Mg2+-ATPase...
January 2006: Ukraïnsʹkyĭ Biokhimichnyĭ Z︠h︡urnal
De-Zai Dai
CPU86017 is a novel Class III antiarrhythmic agent derived from berberine and with an improved pharmacological profile, solubility and bioavailability. It is active in suppressing arrhythmias in several animal models. The ED(50) of CPU86017 for suppressing ischemia/reperfusion arrhythmias in rats was 0.22 mg/kg against 2.23 mg/kg for lidocaine. CPU86017 is about 10-fold more potent than lidocaine. It blocks I(K(R.tail)), I(K(S)), and I(Ca(L)) currents with IC(50) values of 25, 14.4, and 11.5 microM, respectively...
2006: Cardiovascular Drug Reviews
Detlef Bieger, Kakoli Parai, Carol Ann Ford, Reza Tabrizchi
The effect of isoprenaline on tone, cyclic adenosine 3':5' monophosphate (cAMP), and smooth muscle membrane potential (E ( m )) were assessed in rat isolated pulmonary arteries. N(omega)-nitro-L-arginine methyl ester (10.0 microM) or removal of endothelium partially inhibited relaxant responses to isoprenaline, but glibenclamide (10.0 microM) and indomethacin (10.0 microM) did not. While Rp-8-Br-cAMP (30.0 microM), tetraethylammonium (0.3 & 1.0 mM), 4-aminopyridine (100 microM), anandamide (10.0 microM), charybdotoxin (0...
June 2006: Naunyn-Schmiedeberg's Archives of Pharmacology
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