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.
An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.
A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose.
The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.
A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)
An element that is an alkali metal. It has an atomic symbol Rb, atomic number 37, and atomic weight 85.47. It is used as a chemical reagent and in the manufacture of photoelectric cells.
A cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665)
Unstable isotopes of rubidium that decay or disintegrate emitting radiation. Rb atoms with atomic weights 79-84, and 86-95 are radioactive rubidium isotopes.
Stable sodium atoms that have the same atomic number as the element sodium, but differ in atomic weight. Na-23 is a stable sodium isotope.
A number of different cardioactive glycosides obtained from Strophanthus species. OUABAIN is from S. gratus and CYMARINE from S. kombe. They are used like the digitalis glycosides.
Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).
Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis.
A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycone moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose.
Cyclopentanophenanthrenes with a 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. They are found in BUFONIDAE and often possess cardiotonic properties.
A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.
An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The aglycone constituents of CARDIAC GLYCOSIDES. The ring structure is basically a cyclopentanoperhydrophenanthrene nucleus attached to a lactone ring at the C-17 position.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
Stable potassium atoms that have the same atomic number as the element potassium, but differ in atomic weight. K-41 is a stable potassium isotope.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An alpha-2 selective adrenergic agonist used as an antihypertensive agent.
A sulfamyl diuretic.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
The scientific discipline concerned with the physiology of the nervous system.
A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
Those individuals engaged in research.
An opisthobranch mollusk of the order Anaspidea. It is used frequently in studies of nervous system development because of its large identifiable neurons. Aplysiatoxin and its derivatives are not biosynthesized by Aplysia, but acquired by ingestion of Lyngbya (seaweed) species.
Financial support of research activities.
A class in the phylum MOLLUSCA comprised of SNAILS and slugs. The former have coiled external shells and the latter usually lack shells.
A diet which contains very little sodium chloride. It is prescribed by some for hypertension and for edematous states. (Dorland, 27th ed)
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.

PST 2238: A new antihypertensive compound that modulates Na,K-ATPase in genetic hypertension. (1/3013)

A genetic alteration in the adducin genes is associated with hypertension and up-regulation of the expression of renal Na, K-ATPase in Milan-hypertensive (MHS) rats, in which increased ouabain-like factor (OLF) levels are also observed. PST 2238, a new antihypertensive compound that antagonizes the pressor effect of ouabain in vivo and normalizes ouabain-dependent up-regulation of the renal Na-K pump, was evaluated for its ability to lower blood pressure and regulate renal Na,K-ATPase activity in MHS genetic hypertension. In this study, we show that PST 2238, given orally at very low doses (1 and 10 microg/kg for 5-6 weeks), reduced the development of hypertension in MHS rats and normalized the increased renal Na,K-ATPase activity and mRNA levels, whereas it did not affect either blood pressure or Na,K-ATPase in Milan-normotensive (MNS) rats. In addition, a similar antihypertensive effect was observed in adult MHS rats after a short-term treatment. In cultured rat renal cells with increased Na-K pump activity at Vmax due to overexpression of the hypertensive variant of adducin, 5 days of incubation with PST 2238 (10(-10-)-10(-9) M) lowered the pump rate to the level of normal wild-type cells, which in turn were not affected by the drug. In conclusion, PST 2238 is a very potent compound that in MHS rats reduces blood pressure and normalizes Na-K pump alterations caused by a genetic alteration of the cytoskeletal adducin. Because adducin gene mutations have been associated with human essential hypertension, it is suggested that PST 2238 may display greater antihypertensive activity in those patients carrying such a genetic alteration.  (+info)

Fluid secretion by the malpighian tubules of the tsetse fly Glossina morsitans: the effects of ouabain, ethacrynic acid and amiloride. (2/3013)

The effects of three inhibitors of sodium transport on the secretion of fluid by the Malpighian tubules of Glossina morsitans have been observed. The cardiac glycoside, ouabain, affects neither the rate of secretion nor the sodium concentration of the fluid secreted when isolated tubules are bathed by solutions containing a range of sodium and potassium concentrations. Secretion is inhibited, however, by ethacrynic acid and amiloride. The results confirm that fluid secretion by the Malpighian tubules of this insect is dependent on the active transport of sodium ions and show that Na+/k+ exchange pumps are not involved in this process.  (+info)

Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats. (3/3013)

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3',-5-triiodo-L-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.  (+info)

A chimeric gastric H+,K+-ATPase inhibitable with both ouabain and SCH 28080. (4/3013)

2-Methyl-8-(phenylmethoxy)imidazo(1,2-a)pyridine-3acetonitrile+ ++ (SCH 28080) is a K+ site inhibitor specific for gastric H+,K+-ATPase and seems to be a counterpart of ouabain for Na+,K+-ATPase from the viewpoint of reaction pattern (i.e. reversible binding, K+ antagonism, and binding on the extracellular side). In this study, we constructed several chimeric molecules between H+,K+-ATPase and Na+,K+-ATPase alpha-subunits by using rabbit H+,K+-ATPase as a parental molecule. We found that the entire extracellular loop 1 segment between the first and second transmembrane segments (M1 and M2) and the luminal half of the M1 transmembrane segment of H+, K+-ATPase alpha-subunit were exchangeable with those of Na+, K+-ATPase, respectively, preserving H+,K+-ATPase activity, and that these segments are not essential for SCH 28080 binding. We found that several amino acid residues, including Glu-822, Thr-825, and Pro-829 in the M6 segment of H+,K+-ATPase alpha-subunit are involved in determining the affinity for this inhibitor. Furthermore, we found that a chimeric H+,K+-ATPase acquired ouabain sensitivity and maintained SCH 28080 sensitivity when the loop 1 segment and Cys-815 in the loop 3 segment of the H+,K+-ATPase alpha-subunit were simultaneously replaced by the corresponding segment and amino acid residue (Thr) of Na+,K+-ATPase, respectively, indicating that the binding sites of ouabain and SCH 28080 are separate. In this H+, K+-ATPase chimera, 12 amino acid residues in M1, M4, and loop 1-4 that have been suggested to be involved in ouabain binding of Na+, K+-ATPase alpha-subunit are present; however, the low ouabain sensitivity indicates the possibility that the sensitivity may be increased by additional amino acid substitutions, which shift the overall structural integrity of this chimeric H+,K+-ATPase toward that of Na+,K+-ATPase.  (+info)

Multiple mechanisms confer drug resistance to mitoxantrone in the human 8226 myeloma cell line. (5/3013)

Selection for in vitro drug resistance can result in a complex phenotype with more than one mechanism of resistance emerging concurrently or sequentially. We examined emerging mechanisms of drug resistance during selection with mitoxantrone in the human myeloma cell line 8226. A novel transport mechanism appeared early in the selection process that was associated with a 10-fold resistance to mitoxantrone in the 8226/MR4 cell line. The reduction in intracellular drug concentration was ATP-dependent and ouabain-insensitive. The 8226/MR4 cell line was 34-fold cross-resistant to the fluorescent aza-anthrapyrazole BBR 3390. The resistance to BBR 3390 coincided with a 50% reduction in intracellular drug concentration. Confocal microscopy using BBR 3390 revealed a 64% decrease in the nuclear:cytoplasmic ratio in the drug-resistant cell line. The reduction in intracellular drug concentration of both mitoxantrone and BBR 3390 was reversed by a novel chemosensitizing agent, fumitremorgin C. In contrast, fumitremorgin C had no effect on resistance to mitoxantrone or BBR 3390 in the P-glycoprotein-positive 8226/DOX6 cell line. Increasing the degree of resistance to mitoxantrone in the 8226 cell line from 10 to 37 times (8226/MR20) did not further reduce the intracellular drug concentration. However, the 8226/MR20 cell line exhibited 88 and 70% reductions in topoisomerase II beta and alpha expression, respectively, compared with the parental drug sensitive cell line. This decrease in topoisomerase expression and activity was not observed in the low-level drug-resistant, 8226/MR4 cell line. These data demonstrate that low-level mitoxantrone resistance is due to the presence of a novel, energy-dependent drug efflux pump similar to P-glycoprotein and multidrug resistance-associated protein. Reversal of resistance by blocking drug efflux with fumitremorgin C should allow for functional analysis of this novel transporter in cancer cell lines or clinical tumor samples. Increased resistance to mitoxantrone may result from reduced intracellular drug accumulation, altered nuclear/cytoplasmic drug distribution, and alterations in topoisomerase II activity.  (+info)

Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro. (6/3013)

AIM: To study the direct effect of enalapril on cellular electrophysiology of myocardium. METHODS: Conventional microelectrodes technique was used to record the action potentials (AP) of guinea pig papillary muscles. RESULTS: Enalapril caused an increase of the AP amplitude (APA) and the resting potential (RP) in a concentration-dependent manner without any significant change of AP duration, Vmax and overshoot of AP. Superfusion of ouabain 0.5 mumol.L-1 reduced APA and RP, induced stable delayed after-depolarizations (DAD) at different basic cycle lengths (BCL) in a frequency-dependent manner. At BCL 200 ms, the amplitude of DAD was large enough to induce nonsustained triggered activity (TA). In additional presence of enalapril 10 mumol.L-1, the DAD amplitude at 500, 400, 300, and 200 ms were decreased from 5.3 +/- 2.3, 5.9 +/- 2.8, 7.4 +/- 2.1, and 8.9 +/- 1.3 to 2.6 +/- 0.7, 3.1 +/- 1.0, 3.7 +/- 1.5, and 5.3 +/- 1.1 (mV) respectively, all P < 0.01. The compensation intervals were increased in a similar frequency-dependent manner. The number of TA induced at BCL 200 ms was decreased from 3.6 +/- 0.7 to 0.8 +/- 0.2 (P < 0.05). CONCLUSION: Enalapril directly inhibits DAD and TA induced by ouabain through increasing RP and APA, which may contribute to its anti-arrhythmic effect.  (+info)

Role of K+ channels in A2A adenosine receptor-mediated dilation of the pressurized renal arcuate artery. (7/3013)

1. Adenosine A2A receptor-mediated renal vasodilation was investigated by measuring the lumenal diameter of pressurized renal arcuate arteries isolated from the rabbit. 2. The selective A2A receptor agonist CGS21680 dilated the arteries with an EC50 of 130 nM. The CGS21680-induced vasodilation was, on average, 34% less in endothelium-denuded arteries. 3. The maximum response and the EC50 for CGS21680-induced vasodilation in endothelium-intact arteries were not significantly affected by incubation with the K+ channel blockers apamin (100 nM), iberiotoxin (100 nM), 3,4-diaminopyridine (1 mM), glibenclamide (1 microM) or Ba2+ (10 microM). However, a cocktail mixture of these blockers did significantly inhibit the maximum response by almost 40%, and 1 mM Ba2+ alone or 1 mM Ba2+ in addition to the cocktail inhibited the maximum CGS21680-response by 58% and about 75% respectively. 4. CGS21680-induced vasodilation was strongly inhibited when the extracellular K+ level was raised to 20 mM even though the dilator response to 1 microM levcromakalim, a K(ATP) channel opener drug, was unaffected. 5. CGS21680-induced vasodilation was inhibited by 10 microM ouabain, an inhibitor of Na+/K(+)-ATPase, but ouabain had a similar inhibitory effect on vasodilation induced by 30 nM nicardipine (a dihydropyridine Ca2+ antagonist) or 1 microM levcromakalim. 6. The data suggest that K+ channel activation does play a role in A(2A) receptor-mediated renal vasodilation. The inhibitory effect of raised extracellular K+ levels on the A(2A) response may be due to K(+)-induced stimulation of Na+/K(+)-ATPase.  (+info)

Excretion of taurocholate from isolated hepatocytes. (8/3013)

Efflux of taurocholate from isolated rat hepatocytes was studied to characterize the mechanism of bile acid secretion. Cells were incubated with taurocholate for 15 min. The amount of the intracellularly accumulated bile acid was directly related to the concentration in the medium. Transfer of the loaded cells from the incubation medium to a medium without taurocholate led to taurocholate efflux. Efflux was saturable, its activation energy amounted to 12 kcal/mol (50 kJ). It was strongly inhibited by the metabolic inhibitor antimycin A and to a lesser extend by the uncoupler carbonylcyanide-m-chlorophenylhydrazone. Dinitrofluorobenzene and mersalyl, reagents which react with amino acids, inhibited efflux by about 30% when applied at concentrations of 50 muM. Ouabain increased the rate of efflux. The observations indicate that secretory functions are maintained in isolated liver cells.  (+info)

The effects of ouabain or ouabain and furosemide on renal function and renin secretion were studied in conscious isovolemic sheep. The sheep received a continuous renal arterial infusion of papaverine, 7 mg/min, throughout the experiment. Ouabain alone (7 X 10(-7) M in the renal plasma) produced significant decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF) but not in renal perfusion pressure. Plasma [K+] rose after ouabain administration. Fractional (FENa) and absolute (UNaV) Na+ excretion were 2.9 +/- 1.0% (mean +/- SE) and 78 +/- 54 muEq/min, respectively, during the papaverine infusion and rose to 19 +/- 5.1% (P less than 0.05) and 528 +/- 116 muEq/min (P less than 0.01) after ouabain administration. Despite the large changes in Na+ reabsorption, renin secretion was not stimulated. During the control period, renin secretion was 281 +/- 131 ng/min and the average renin secretion after ouabain administration was 310 +/- 78 ng/min (not significant). A smaller dose of ...
Changes in the sodium/potassium-adenosine triphosphatase (Na+/K+ pump) of human leukocytes may reflect changes in the Na+/K+ pump of vascular smooth muscle cells in cryptogenic (essential) hypertension. Lymphocytes from healthy donors have significantly fewer Na+/K+ pumps than normal when incubated for 72 h with serum from patients with crytogenic hypertension. This effect might be due to Na+/K+ pump inhibition by a cardiac glycoside-like substance in the serum. We assessed the sensitivity of two techniques for measuring inhibition of cellular (Na+/K+ pumps by ouabain at low concentrations in vitro. We incubated lymphocytes from healthy subjects for 1 h and 72 h with unlabelled ouabain at different concentrations to determine the lowest concentration which inhibits specific 3H-ouabain binding (the number of Na+/K+ pumps) and ouabain sensitive 86rubidium influx (pump activity). Incubation of cells with ouabain for 1 h did not significantly affect Na+/K+ pump activity. The lowest ouabain ...
1. The influence of single-dose intravenous ouabain on haemodynamics, renal function and vasoactive hormones was investigated in healthy subjects.. 2. After ouabain injection there was a significant reduction in minimum and average hourly heart rates. Diastolic blood pressure fell immediately after ouabain, without a significant change in systolic blood pressure.. 3. There was no change in renal blood flow, glomerular filtration rate, hourly urine volume or sodium and potassium excretion.. 4. Ouabain injection was associated with a fall in plasma angiotensin II levels and a rise in plasma adrenaline levels, but plasma noradrenaline levels were unchanged. Both plasma atrial and brain natriuretic peptide levels were increased after ouabain administration.. 5. The present study demonstrates that ouabain has significant although minor, acute effects on plasma levels of vasoactive hormones. It fails, however, to confirm that ouabain is an acute pressor or natriuretic substance. If it has an important ...
TY - JOUR. T1 - Quantification of Rat Cerebral Cortex Na+,K+‐ATPase. T2 - Effect of Age and Potassium Depletion. AU - Schmidt, Thomas Andersen. AU - Larsen, Jim Stenfatt. AU - Kjeldsen, Keld. PY - 1992/12. Y1 - 1992/12. N2 - Abstract: Na+,K+‐ATPase concentration in rat cerebral cortex was studied by vanadate‐facilitated [3H]ouabain binding to intact samples and by K+‐dependent 3‐O‐methylfluorescein phosphatase activity determinations in crude homogenates. Methodological errors of both methods were evaluated. [3H]Ouabain binding to cerebral cortex obtained from 12‐week‐old rats measured incubating samples in buffer containing [3H]ouabain, and ouabain at a final concentration of 1 × 10-6 mol/L gave a value of 11,351 ± 177 (n = 5) pmol/g wet weight (mean ± SEM) without any significant variation between the lobes. Evaluation of affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. K+‐dependent 3‐O‐methylfluorescein phosphatase ...
Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2-3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys
Ouabain, that has been isolated from bovine adrenals and hypothalamus, is a new cardiotonic steroid hormone, which is either synthesized in the adrenals or stored there after it has absorbed from the diet. Little is known ,i,in vivo,/i, which events may lead to the release of ouabain into blood. Moreover, a binding protein for cardiotonic steroids exists in blood, which binds cardiac glycosides with high affinity. It may affect the action of endogenous ouabain on heart and circulation, but the physiological function of this protein is unclear. To realize, which physiological stimuli ,i,in vivo,/i, may affect blood concentrations of endogenous ouabain and which function the cardiotonic binding protein may have in modulating ouabain effects, the effect of physical exercise on endogenous ouabain was studied and the tissue distribution of its binding protein was investigated. We found that endogenous ouabain changes rapidly in blood upon physical exercise and behaves like expected for a hormone of ...
An enzyme-linked immunosorbent assay is described for the measurement of ouabain in human plasma. This assay is specific for ouabain, strophanthidin, and ouabagenin, with other steroids, including digoxin and vasopressor hormones, exhibiting negligible cross-reactivity. Assay sensitivity was 0.06 nmol/L if 1 mL plasma was extracted and less than 0.005 nmol/L when 20 mL plasma was analyzed. Extracted plasma samples showed ouabainlike immunoreactivity that diluted in parallel with the ouabain standard curve. Repeated extraction and assay of single plasma samples, however, did not produce consistent results in the assay. Increased specificity was obtained by high-performance liquid chromatography of sample extracts before assay. When high-performance liquid chromatographic profiles of plasma spiked with ouabain standard or following bolus intravenous injections of ouabain into normal human volunteers were compared with profiles of unspiked plasma, there was no support for the immunoreactive ...
The response of the left ventricle to a level of supine bicycle exercise that induced angina, and the effects of ouabain (0.01 mg/kg) on this response were evaluated in 14 patients with coronary arterial disease. Before administration of ouabain, exercise was associated with depressed pumping performance of the left ventricle in four patients: stroke work fell with exercise while left ventricular end-diastolic pressure (LVEDP) increased. In five patients left ventricular (LV) performance was not frankly depressed, but nevertheless was abnormal: stroke work increased, but was accompanied by an inordinately large rise in LVEDP. In the remaining five patients LV function was essentially normal. Ouabain improved LV performance at rest in only a minority of patients, but during the stress of exercise, LV hemodynamics were improved by ouabain in 12 of the 14 patients. Five patients, however, continued to show either depressed or abnormal function with exercise after they were given ouabain. As judged ...
By using random mutagenesis (for references, see Croyle et al., 1997) or chimeras between Na,K- and H,K-ATPase (Qiu et al., 2003), nearly 20 amino acids have been identified that influence the sensitivity of Na,K-ATPase to ouabain. These amino acids are located in several transmembrane segments and extracellular loops of the Na,K-ATPase α-subunit and are hypothesized to comprise the physical binding site or to affect indirectly ouabain binding by conformational changes. In this study, we have investigated the structural determinants that are responsible for the α isoform-specific differences in the ouabain binding kinetics and could identify new amino acids that are involved in ouabain binding and play a role in the access and release of ouabain to and from its binding site.. Results from previous kinetic studies of ouabain binding, which were performed mainly on Na,K-ATPase α1 isozymes, have suggested that the rate of association of ouabain to enzymes from different sources, both sensitive ...
1. The cardiac glycoside ouabain, in concentrations ranging from 2 to 3 x 10-7, increases the oxygen uptake of slices of guinea pig heart muscle in the presence of glucose or lactate; at higher concentrations this increase (maximally 50 per cent) is followed by a depression (maximally 80 per cent). Among a variety of other guinea pig tissues studied, brain cortex alone responds in a similar manner, but is only about ⅕ as sensitive as heart muscle.. 2. The oxidation of Succinate in cardiac slices is not inhibited at all by ouabain; in brain cortex slices it is inhibited only to a moderate extent. In the presence of pyruvate, the oxygen uptake of cardiac slices, which is high initially, is depressed by ouabain without preceding stimulation. The effect of the drug on the oxygen uptake of brain cortex slices is the same in pyruvate as in glucose or lactate medium.. 3. The increase in the respiration of cardiac slices produced by ouabain is dependent upon the presence and concentration of ...
Ouabain, a specific inhibitor of active cation transport across cell membrane, was applied topically to brain surface of cats. The cerebral cortex to which 10−3M ouabain was applied showed a spongy...
Langham, Maurice E., and Kenneth E. Eakin. THE INFLUENCE OF THE CARDIAC GLYCOSIDE OUABAIN ON THE INTRAOCULAR PRESSURE AND DYNAMICS OF THE RABBIT AND THE CAT. Journal of Pharmacology and Experimental Therapeutics 144.3 (1964): 421-428. Web. 12 Dec. 2017. ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Magnesium atom in PDB 3b8e: Crystal Structure of the Sodium-Potassium Pump
TY - JOUR. T1 - Calcium and contractile responses to ouabain in aortae from spontaneously hypertensive rats (SHR). AU - Lamb, F. S.. AU - Moreland, R. S.. AU - Webb, R. C.. PY - 1984. Y1 - 1984. UR - http://www.scopus.com/inward/record.url?scp=17944387233&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=17944387233&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:17944387233. VL - 43. SP - no. 834. JO - Federation Proceedings. JF - Federation Proceedings. SN - 0014-9446. IS - 3. ER - ...
In the brain at least 40% of the energy produced by mitochondrial respiration is required by the Na+/K+-ATPase to maintain ion gradients across the cell membranes. Energy levels in the brain can be compromised by a lack of glucose and oxygen or by defects in the respiratory chain such as occurring in stroke and Parkinsons disease, respectively. Na+/K+-ATPase function is inhibited during energy failure. This may lead to a prolonged depolarization of the neuron, excessive release, and reversal of the uptake of excitatory amino acids, i.e., the induction of excitotoxicity (Dirnagl et al., 1999; Doble, 1999; Nicotera et al., 1999). Ouabain inhibits Na+/K+-ATPases and is a very potent neurotoxin that leads to pancellular necrosis and infarction (Lees, 1991). It is used to study the involvement of Na+/K+-ATPase in CNS pathology (Lees et al., 1990; Lees, 1991; Lees and Leong, 1994,1995; Stelmashook et al., 1999). Ouabain rapidly perturbs ion homeostasis and induces cell swelling and ...
The function of ouabain to act as a signal generator of the sodium pump opens up new therapeutic options and illustrates the therapeutic potential of ouabain
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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 calf serum and human serum contain a dialysable factor or factors which stimulate specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes.. 4. To further elucidate the mechanisms underlying these changes we also measured the activity of two other enzymes of the lymphocyte plasma membrane, 5′-nucleotidase and γ-glutamyltransferase, the uptake of [3H]thymidine by ...
TY - JOUR. T1 - Suppression and potentiation of mouse hematopoietic progenitor cell proliferation by ouabain. AU - Spivak, J. L.. AU - Misiti, J.. AU - Stuart, R.. AU - Sharkis, S. J.. AU - Sensenbrenner, L. L.. PY - 1980. Y1 - 1980. N2 - Clonal assays for CFU-S, CFU-C, BFU-E, and CFU-E were employed to evaluate the effect of ouabain on the proliferation of mouse hematopoietic progenitor cells. Preincubation of bone marrow cells with ouabain at concentrations of 10-6-10-12 M suppressed the proliferation of CFU-S as measured by the spleen colony assay. At 10-9 M ouabain, spleen colony formation was inhibited by more than 95%. When included in soft agar cultures of bone marrow cells, ouabain suppressed the proliferation of CFU-C in a complex fashion. At 10-4 M ouabain, colony formation was suppressed by 70%, while at 10-6 M ouabain, CFU-C proliferation was normal. At 10-9 M ouabain, however, the number of colonies formed was only 70% of normal, and complete recovery was not obtained at 10-12 M ...
The effect of cardiac glycosides to increase cardiac inotropy by altering Ca2+ cycling is well known but still poorly understood. The studies described in this report focus on defining the effects of ouabain signaling on sarcoplasmic reticulum Ca2+-ATPase function. Rat cardiac myocytes treated with 50 μM ouabain demonstrated substantial increases in systolic and diastolic Ca2+ concentrations. The recovery time constant for the Ca2+ transient, τ, was significantly prolonged by ouabain. Exposure to 10 μM H2O2, which causes an increase in intracellular reactive oxygen species similar to that of 50 μM ouabain, caused a similar increase in τ. Concurrent exposure to 10 mM N-acetylcysteine or an aqueous extract from green tea (50 mg/ml) both prevented the increases in τ as well as the changes in systolic or diastolic Ca2+ concentrations. We also observed that 50 μM ouabain induced increases in developed pressure in addition to diastolic dysfunction in the isolated perfused rat heart. Coadministration of
Digitalis glycosides are major tools for the identification of the Na/K ATPase as well as the Na/K fluxes mediated by this transport system. Since its discovery 50 yr ago (Schatzmann, 1953), the inhibitory effect of these compounds on the Na/K pump has been confirmed repeatedly. There has been evidence to contrary effects, although. Thus, Hougen et al. (1981) reported a stimulatory effect of nanomolar concentrations of ouabain on 86Rb uptake in guinea pig atria. This effect could be suppressed by propranolol, or by prior depletion of endogenous pools of norepinephrine in the tissue, and it was regarded as an indirect effect elicited by norepinephrine released by an action of ouabain on nerve endings in the heart.. Several others have reported stimulating effects of low concentrations of cardiac glycosides on active Na/K transport in multicellular cardiac preparations, and also in the squid axon, it was noted that the inhibitory effect of ouabain on 22Na efflux was preceded by an up to 20% ...
TY - JOUR. T1 - Impact of neonatal treatment with cardioactive glycosides (digoxin, ouabain) on receptor binding capacity, blood level and cardiac function in the adult rat. Extension of the imprinting theory. AU - Csaba, G.. AU - Inczefi-Gonda, Ágnes. AU - Dobozy, O.. AU - Varró, A.. AU - Rablóczky, G.. PY - 1983. Y1 - 1983. N2 - 1. 1. A single neonatal treatment with a cardioactive glycoside (ouabain, digoxin) altered the response of the adult rat to digitaloid treatment. 2. 2. As demonstrated by RIA, re-exposure to digoxin at 2 months of age was followed within 30 min by a more than twofold increase in serum digoxin over the not pretreated control and, although a steady concentration decrease followed, the experimental rats still had a higher serum digoxin level than the controls at 4 h. 3. 3. In the not presensitized control group the serum digoxin peak appeared at 60 min at a considerably lower level than the 30-min maximum of the experimental rats. 4. 4. Neonatal pretreatment with ...
Urinary concentration of OLS was measured by a radioimmunoassay as described previously.22 Briefly, ouabain was conjugated to ovalbumin and keyhole limpet haemocyanin (KLH) and antisera to ouabain was raised in goats by injecting ouabain-ovalbumin and then boosting with ouabain-KLH conjugate. The antisera showed minimal cross-reactivity against ouabagenin (4%) and other related steroids. Tritiated ouabain ([21-22-3H]-ouabain, specific activity approximately 47 μCi/mmol), was diluted to 0.3 μCi/mL with assay buffer (phosphate-buffered saline, 0.1 mol/L, pH 7.4, containing 0.1% bovine serum albumin). Aliquots of 100 μL each of tracer solution, antiserum (final dilution 1:90 000), and urine or standard ouabain were added to polystyrene tubes. After mixing, the reaction mixture was incubated for 1 hour at 37°C or overnight at 4°C. The bound and free ouabains were then separated by adding 250 μL of cold 2.5% dextran-coated charcoal. The samples were mixed, allowed to stand for 10 to 15 minutes ...
Ouabain-like inhibitors are elevated in approximately 50% of patients with essential hypertension and patients with pregnancy-induced hypertension. These materials inhibit the alpha-2 isoform of the Na/K-ATPase in vascular myocytes and increase intracellular sodium levels. The latter enhances calcium entry mediated by the Na/Ca Exchanger (NCX) and results in increased blood pressure. Indeed, prolonged administration of ouabain induces hypertension in Sprague Dawley rats. Paradoxically, normal pregnancy is also associated with an increase in ouabain-like inhibitors, yet blood pressure decreases. My research is focused on the mechanism by which normal pregnant rats become resistant to ouabain-induced hypertension, and the role of NCX and pregnancy hormones in mediating this effect.. ...
Ubiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects that were dependent on the presence of the neuromodulator dopamine. Conversely, activating the pump with the sodium ionophore monensin decreased burst frequency. When more natural locomotor output was evoked using dorsal-root stimulation, ouabain increased burst frequency and extended locomotor episode duration, whereas monensin slowed and shortened episodes. Decreasing the time between dorsal-root stimulation, and therefore interepisode interval, also ...
Arterial myocytes express α1-catalytic subunit isoform Na+ pumps (75-80% of total) which are ouabain resistant in rodents and high ouabain affinity α2-Na+ pumps. affect BP and vasoconstriction. α2SM-DN mice acquired elevated basal indicate BP (indicate Ondansetron (Zofran) BP by telemetry: 117 ± 4 vs. 106 ± 1 mmHg = 7/7 < 0.01) and enhanced BP replies to chronic ANG II infusion (240 ng·kg?1·min?1) and high (6%) NaCl. Many arterial Ca2+ transporters including Na+/Ca2+ exchanger 1 (NCX1) and sarcoplasmic reticulum and plasma membrane Ca2+ pushes [sarco(endo)plasmic reticulum Ondansetron (Zofran) Ca2+-ATPase 2 (SERCA2) and plasma membrane Ca2+-ATPase 1 (PMCA1)] had been also Continue Reading. ...
Showcase your wry biological / biochemical side with a dose of educational, scientific fun with any of these gifts featuring the sodium-potassium pump used in active transport along with the following saying: Stamp Out Imbalance Support Active Transport. Memorable gifts for all who know about the importance of osmoregulation ...
How can more molecules be transported into areas with high concentrations of the molecule? Cells often need to create concentration gradients across membranes. The concentration of a molecule is much higher on one side of the membrane than the other when a concentration gradient exists. In order to create or maintain a concentration gradient, individual molecules must be moved from an area of low concentration to an area of high concentration. This cannot occur through passive diffusion, in fact diffusion will cause the gradient to break down. Only active transport, which requires both specialized transport molecules and the expenditure of energy can drive molecules up a concentration gradient. The sodium potassium pump is an important and well understood example of active transport. View the animation below, then complete the quiz to test your knowledge of the concept.. ...
Levental, M and Tabakoff, B, Sodium-potassium-activated adenosine triphosphatase activity as a measure of neuronal membrane characteristics in ethanol-tolerant mice. (1980). Subject Strain Bibliography 1980. 2608 ...
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IntroductionOuabain (G-Strophanthin) inhibits the activity of Na-K activated adenosinetriphosphatase (ATPase) in in vitro and in vivo systems.1-3 The active tra
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Amaç: Bu çalışmada, basit horlama veya hafif derecede obstrüktif uyku apnesi (OUA) bulunan hastalarda yumuşak damağa radyofrekans doku ablasyonu (RFDA) uygulamasının erken dönemde horlama şiddeti, apne indeksi ve gündüz uykululuk haline etkileri değerlendirildi. Hastalar ve Yöntemler: Çalışmaya apnesiz basit horlaması olan 61, apne indeksi (Aİ) ≤5 ile basit horlaması olan 13 ve hafif derecede OUA (5 ...
Honestly, not as crazy as you might think. During any big dinner gathering, we utilize our dogs place skills. That means we give the dogs a designated area where they must stay until released. We often use place beds for this, but sometimes substitute crates or dog beds (even the couch). We typically put all the dogs in a place right before setting the table. After we have all had our fill, we free the dogs as a group. From here we usually designate one person to hand out goodies one at a time to the pups. Because we stick to this routine time and time again, it goes off flawlessly more often than not ...
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Ray P, Rolek D. The reversal by taurine of ouabain-induced arrhythmias and hypoglycemia. J Am Osteopath Assoc 1975;75(2):211. doi: .. Download citation file:. ...
1. Erythrocyte sodium, sodium transport (ouabain-sensitive efflux rate of sodium, oMosNa, and ouabain-sensitive efflux rate constant of sodium, oMosNa), sodium-potassium activated ouabain-sensitive adenosine triphosphatase (Na+, K+-ATPase) activity and [3H]ouabain-binding capacity were measured in 15 patients with chronic renal failure and in 10 healthy subjects.. 2. As a group, patients with chronic renal failure had a lower erythrocyte sodium and oMosNa compared with healthy subjects.. 3. When patients were divided according to their erythrocyte sodium (greater or less than 4 mmol/kg of cells), in the group of patients whose erythrocyte sodium was less than 4 mmol/kg of cells (group A) the oMosNa was higher than that in healthy subjects and the oMosNa, Na+, K+-ATPase activity and [3H]ouabain-binding capacity were the same as those in healthy subjects. In the subgroup of patients with renal failure whose erythrocyte sodium content was greater than 4 mmol/kg of cells (group B) the oMosNa was ...
Staphylococcus aureus is a notorious pathogen which often causes nosocomial and community attained infections. These infections steadily increased after evolving the resistance due to indecorous practice of antibiotics and now become a serious health issue. Ouabain is a Na+/K+-ATPase inhibitor that leads to increase the heart contraction in patients with congestive heart failure. In the present study, in vitro antimicrobial effect of ouabain together with aminoglycosides was determined against clinical and non-clinical S. aureus strains. Using checkerboard, Gentamycin uptake and biofilm assays, we analysed he interactions of ouabain with aminoglycosides. Ouabain induced the staphylocidal potency of aminoglycosides by remarkably reducing the MIC of gentamycin (GEN) by 16 (0.25 μg/mL), 8 folds (0.5 μg/mL) amikacin (AMK); and 16 folds (1.0 μg/mL) with kanamycin (KAN), compared to their individual doses. OBN severely reduced cell viability within 60 min with GEN (1 μg/mL), KAN (2 μg/mL) and 90 min with
The Na+ K+-ATPase pump maintains the gradient of a higher concentration of sodium extracellularly and a higher level of potassium intracellularly. The sodiumâ potassium pump is found in many cell (plasma) membranes. The sodium/potassium ATPase pump is essential to many physiological processes, and so targeting it with medication can be useful clinically. Explore the sodium potassium pump (Na+/K+ pump), with the Amoeba Sisters! Examples of â ¦ It also involves being conscious of every hint of flavoring in your food and how you cook your meals. In the kidneys, sodium and potassium have a reciprocal relationship. Na+-K+ pump in chronic renal failure. In a single cycle of the pump, three sodium ions are extruded from and two potassium â ¦ Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. Acting on the distal tubules, the hormone aldosterone triggers potassium excretion and resorption of sodium. Conversely, drugs which act ...
Sodium-potassium pump definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up now!
The plant-derived steroid, digoxin, a specific inhibitor of Na,K-ATPase, has been used for centuries in the treatment of heart disease. Recent studies demonstrate the presence of a digoxin analog, ouabain, in mammalian tissue, but its biological role has not been elucidated. Here, we show in renal epithelial cells that ouabain, in doses causing only partial Na,K-ATPase inhibition, acts as a biological inducer of regular, low-frequency intracellular calcium ([Ca2+](i)) oscillations that elicit activation of the transcription factor, NF-KB. Partial inhibition of Na,K-ATPase using low extracellular K+ and depolarization of cells did not have these effects. Incubation of cells in Ca2+-free media, inhibition of voltage-gated calcium channels, inositol triphosphate receptor antagonism, and redistribution of actin to a thick layer adjacent to the plasma membrane abolished [Ca2+](i) oscillations, indicating that they were caused by a concerted action of inositol triphosphate receptors and capacitative ...
Studies were performed on Na and K transport by red blood cells of the freshwater turtle under anaerobic and aerobic conditions. Although it had previously been assumed that cation transport in turtle red blood cells was dependent on respiration, the present data show greater Na efflux rates in N2 than in O2. However, ouabain inhibited Na transport by the same amount quantitatively in O2 and N2 gas phases. Thus there was no difference in ouabain-sensitive or pump Na transport rates. Na influx rates were higher in nitrogen than in air and potassium influx rates were not significantly different under aerobic and anaerobic conditions. Moreover in the absence of sodium in the bathing medium no difference between air and nitrogen could be discovered. Finally with ethacrynic acid plus ouabain there was an additional decrease in Na efflux but there was a persisting difference between air and nitrogen. These studies do not rule out the existence of a ouabain-insensitive ethacrynic acid-inhibitable ...
Na+,K+-ATPase is one of the most important proteins in the mammalian cell. It creates sodium and potassium gradients which are fundamental for the membrane potential and sodium-dependent secondary active transport. It has a second role in the cell as a receptor that by binding chemicals from the cardiotonic steroids family, the most knowledgeable of them is ouabain, triggers various signaling pathways in the cell which regulate gene activation, proliferation, apoptosis, etc. It has been shown that several severe neurological diseases are associated with mutations in the Na+,K+-ATPase encoding genes. Although Na+,K+-ATPase was discovered already in 1957 by the Danish scientist Jens Skou, the knowledge about the function of this enzyme is still not complete.. In the studies included in the thesis, we have learned more about the function of Na+,K+-ATPase in different aspects of health and disease. In study I we showed a mechanism of ouabain-dependent regulation of the NMDA receptor, one of the most ...
Canine cancers develop in immunocompetent environments and share many similar features observed in human cancers, such as long periods of latency for initiation, progression and development, metastasis, acquired drug resistance and recurrence. Osteosarcoma is a primary bone tumor that occurs in dogs. It is highly aggressive and metastatic in nature, and the therapeutic methods utilized to treat this primary canine tumor are very limited. We have successfully established canine osteosarcoma orthotopic xenograft models with NSG mice (from Jackson Lab) in vivo. Ouabain, known as Na+, K+ ATPase inhibitor, has been used for many years in human clinical applications for the treatment of congestive heart failure. Recently, ouabain has been investigated for potential anticancer properties. However, the therapeutic dose window is very narrow because the side effects of ouabain overdose can be lethal. In an attempt to mitigate such narrow therapeutic margin of safety, ouabain was formulated in lipid ...
Enhanced Na+/H+ exchange, measured as amiloride derivative-sensitive Na+ and H+ fluxes in cells with a preliminary acidified cytoplasm (Δμ H+-induced Na+/H+ exchange), is one of the most prominent intermediate phenotypes of altered vascular smooth muscle cell (VSMC) function in spontaneously hypertensive rats (SHR). Analysis of Na+/H+ exchange in F2 hybrids of SHR and normotensive rats seems to be the most appropriate approach in the search for the genetic determinants of abnormal activity of this carrier. However, the measurement of Δμ H+-induced Na+/H+ exchange is hardly appropriate for precise analysis of the carriers activity in VSMC derived from several hundred F2 hybrids. To overcome this problem, we compared the rate of 22Na influx under baseline conditions and in Na+-loaded (ouabain-treated) VSMC. The dose-dependency of the rate of Δμ H+-induced H+ efflux as well as of 22Na influx in control and ouabain-treated cells on ethylisopropylamiloride (EIPA) concentration were not ...
Voltage-gated Na+ channels are promising drug targets. Screening of large numbers of putative modulators, however, can be demanding and expensive. In this study, a simple, cheap, and robust assay to test the pharmacological modulation of Na+ channel function is presented. The assay makes use of the fact that the intracellular accumulation of Na+ ions can be cytotoxic. The toxicity of the Na+ channel activator veratridine in the presence of an inhibitor of the Na+/K+ ATPase (ouabain) in a Nav1.2a (rat brain IIA alpha) expressing cell line is assessed. Na+ channel blockers should reduce toxicity in this model. CHO cells which recombinantly expressed rat Nav1.2a subunits were seeded in 96-well plates, and cell survival was tested after 24 h incubation in medium containing veratridine and ouabain in the presence or absence of Na+ channel blockers. Propidium iodide fluorescence was used as toxicity readout. Veratridine (100 microM) or ouabain alone (500 microM) were not toxic to the cells. In the ...
In plants, an example of active transport being used is in the root hair cells of the plant, to move much-needed ions from the soil into the root of the plant. This also causes the water potential within the plant to decrease/become more negative, so more water moves in by osmosis, which is obviously beneficial to the plant. Animals also use active transport in a similar way, to move glucose and other important molecules, present from digested food, from the lumen of the small intestine, into the cells lining it, to be used for respiration, protein production and other processes. Another use of ATP in animals, that plants do not share, is within neurones. Nerve cells/neurones require ATP to provide energy to sodium-potassium pumps, which are embedded in the membrane of the cell body and within the nodes of Ranvier of the axons of (myelinated) neurones. These sodium-potassium pumps are required to achieve and maintain a resting potential before and after action potentials have been generated ...
Both high and low doses of CORT caused a modest depolarization of BLA neurons. Several mechanisms might account for this effect, including the inhibition of the sodium-potassium pump, of the resting K+ conductance, or of a voltage-dependent K+ current activated near rest. Because the membrane depolarization was observed without a significant increase in Rin in the low-dose CORT group, it is more likely that the effect of CORT is mediated by an inhibition of the sodium-potassium pump.. In contrast, the increase in Rin seen with the high dose of CORT probably involved the inhibition of one or more K+ currents such as the K+ leak or of a K+ conductance that is active near rest. Moreover, the fact that the high CORT dose markedly reduced spike-frequency adaptation suggests that CORT also inhibited one or more subtype(s) of voltage-gated or Ca2+-dependent K+ currents that are activated in the suprathreshold range of membrane potentials. In support of this hypothesis, previous studies have revealed ...
The possibility that alveolar macrophages and type-II cells can accumulate taurine was examined. The study involved measuring the taurine content of the cells, the rates of taurine uptake in the presence of a normal plasma concentration of taurine, the concentration dependence and kinetic parameters for the transport system, and the effects of metabolic inhibitors or ouabain on the transport proce
Does anyone leave the insulin pump site in for longer than 3 days or is that a no-no! I know that the sensor can be left in for longer but I did not...
The bottom line effect of this is to make cell effectively impermeable to NaCl. Gibbs Donnan equilibrium do not reached and cell does not swell inspite of the presence of protein ion ...
Our laboratory is interested in the physiological role of the Na,K-ATPase, particularly the function of the different alpha isoforms of this enzyme. The present...
The equilibrated of sodium and potassium from external to the bath governed by rate constant (0.09 ms and 0.05 ms). the governing equation of external included (unsteady term= diffusion flux + membrane flux+ ion access to/into FH space ...
Study: Sodium-to-potassium ratio a key to heart health Sodium-Saturated Diet Is a Threat for All Study Finds Sodium-Potassium Ratio Strongly Tied to
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... is a highly toxic compound with a LD50 of 5 mg/kg when administered orally to rodents. However, ouabain has a low ... Although ouabain is no longer approved for use in the USA, in France and Germany, intravenous ouabain has a long history in the ... Ouabain was seen as a possible treatment for certain cardiac conditions. Strophanthidin "ouabain" in the World English ... Hence, it was suggested that some assays for endogenous ouabain detected other compounds or failed to detect ouabain at all. ...
"The stimulation of phosphate of ouabain binding to the sodium pump..." The Journal of Physiology. 252 (2). 1 November 1975. doi ... Chipperfield, A. R.; Whittam, R. (1973). "Ouabain Binding to the Sodium Pump". Nature. 242 (5392): 62-63. Bibcode:1973Natur.242 ...
Some of the chemicals in the plants are used to produce the drug ouabain, which was taken as a cardiac stimulant to treat heart ... ouabain), k-strophanthin, and e-strophanthin. As ordinarily administered, the drug acts on the heart before influencing any ...
"Resolution of the insect ouabain paradox". Proceedings of the National Academy of Sciences of the United States of America. 101 ...
Furthermore, an ouabain block of Na⁺-K⁺ pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia. ... However, upon subsequent ouabain binding, the Src kinase domain is released and then activated. Based on this scenario, NaKtide ... July 2009). "NaKtide, a Na/K-ATPase-derived peptide Src inhibitor, antagonizes ouabain-activated signal transduction in ... Blaustein MP, Hamlyn JM (December 2010). "Signaling mechanisms that link salt retention to hypertension: endogenous ouabain, ...
Smith, LL (2004). "Oxygen, oxysterols, ouabain, and ozone: a cautionary tale". Free Radical Biology & Medicine. 37 (3): 318-24 ...
It is the aglycone of k-strophanthin, an analogue of ouabain. k-strophanthin is found in the ripe seeds of Strophanthus kombé ... Bruno Kisch (New York City) noted that ouabain (strophanthin-G) has a positive ionotropic activity and faster onset than ... Song H, Karashima E, Hamlyn JM, Blaustein MP (March 2014). "Ouabain-digoxin antagonism in rat arteries and neurones". The ... Ouabain Digoxin Myocardial infarction Toxicity Detoxification Muscle contraction Cardiac glycosides Sigma-Aldrich. " ...
Its sap contains the deadly cardiotoxic glycoside ouabain. The sap is among the most commonly used in arrow poisons, including ...
Ferrari, Patrizia; Ferrandi, Mara; Valentini, Giovanni; Bianchi, Giuseppe (2006). "Rostafuroxin: An ouabain antagonist that ... Ferrari, Patrizia (2010). "Rostafuroxin: An ouabain-inhibitor counteracting specific forms of hypertension". Biochimica et ... corrects renal and vascular Na+-K+- ATPase alterations in ouabain and adducin-dependent hypertension". American Journal of ...
Post asked whether the enzyme was inhibited by ouabain. At this stage Skou was unaware that ouabain inhibited the pump, but he ... Ouabain did indeed inhibit the enzyme, thus establishing a link between the enzyme and the sodium-potassium pump. Following the ... and in his research he had made use of a substance called ouabain (or g-strophanthin) which had recently been shown to inhibit ...
Berova, Nina (1993). "Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus". PNAS. 90 (17): ...
Pitts BJ, Meyerson LR (1981). "Inhibition of Na,K-ATPase Activity and Ouabain Binding by Sanguinarine". Drug Development ...
However, a high dose of ouabain can lead to ventricular tachycardia. C. Andreasen, et al. (2006) Mosby Elsevier, Mosby's ... Third degree AV block can be treated with Cilostazol which acts to increase Ventricular escape rate Ouabain infusion decreases ...
This plant contains ouabain, which is a cardiac glycoside, oleander, and milkweeds. Poisoned arrows are also still used in the ...
Habermann E, Chhatwal GS (1 May 1982). "Ouabain inhibits the increase due to palytoxin of cation permeability of erythrocytes ... where it interacts with the natural binding site of ouabain with very high affinity. Na+/K+-ATPase is a transmembrane protein, ...
September 2021). "Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy". ... ouabain (g-strophanthin) and other strophanthins Digitalis lanata and Digitalis purpurea (Woolly and purple foxglove): digoxin ...
... is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. Antibodies against ... Indeed, an ouabain block of Na+ -K+ pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia. ...
May 2020). "Identification of Atovaquone, Ouabain and Mebendazole as FDA-Approved Drugs Targeting SARS-CoV-2". chemRxiv ( ...
September 2021). "Ouabain and chloroquine trigger senolysis of BRAF-V600E-induced senescent cells by targeting autophagy". ...
"Suppression of ouabain-insensitive K-ATPase activity in rabbit nephron segments during chronic hyperkalemia". Renal Physiology ...
1999). "Ouabain-sensitive H,K-ATPase: tissue-specific expression of the mammalian genes encoding the catalytic alpha subunit". ... This gene encodes a catalytic subunit of the ouabain-sensitive H+/K+ -ATPase that catalyzes the hydrolysis of ATP coupled with ... Sverdlov VE, Kostina MB, Modyanov NN (1997). "Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K- ... "Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase". Genomics. 32 (3): 317-27. doi:10.1006/ ...
"Reducing the Late Sodium Current Improves Cardiac Function during Sodium Pump Inhibition by Ouabain". Journal of Pharmacology ...
... resembles very much other glycosides like ouabain and digoxin but has less effect than digoxin. It is however, just ... like its derivate oleandrigenin, a more potent glycoside than ouabain. Oleandrin and its derivate oleandrigenin are formed in ...
Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. A mutation in the ... Indeed, an ouabain block of Na+ -K+ pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia. ...
"Reducing the Late Sodium Current Improves Cardiac Function during Sodium Pump Inhibition by Ouabain". Journal of Pharmacology ...
The drugs were later publicly identified as digitalis and ouabain, both cardenolide-type cardiac glycosides.) Hicks noted the ...
Furthermore, the presence of a sugar group in ouabain and the absence of one in arenobufagin suggests that it may me more ... along with ouabain. It has been suggested that uncharged and non-polar amino acids may participate in the binding of ... lipophilic that ouabain and as such form a more stable complex with the Na+-K+ pump. Besides its effects on the Na+-K+ pump, ...
"Sodium-dependence and ouabain-sensitivity of the synthesis of dopamine in renal tissues of the rat". Br. J. Pharmacol. 105 (4 ...
They tipped their arrows with ouabain, a poison which caused death by cardiac arrest or respiratory failure. The Maya homeland ...
NEM activates ouabain-insensitive Cl-dependent K efflux in low K sheep and goat red blood cells. This discovery contributed to ...
Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake. In: Hypertension ... Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake. Hypertension. ... Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to Low Sodium Intake. / Lanzani, ... Dive into the research topics of Lanosterol Synthase Gene Polymorphisms and Changes in Endogenous Ouabain in the Response to ...
Role of Mn++ in ouabain induced cardiac arrhythmias.. Authors: Mogre, K M. Nayampalli, S S. Bharadwaj, J. Kashalikar, S J. ... Role of Mn++ in ouabain induced cardiac arrhythmias. Journal of Postgraduate Medicine. 1982 ; 28(4): 194-9. ...
This medicine may cause dizziness, lightheadedness, or fainting, especially when you get up suddenly from a lying or sitting position. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy. If you feel dizzy, lie down so you do not faint. Then sit for a few moments before standing to prevent the dizziness from returning. If you faint, call your doctor right away. Check with your doctor right away if you become sick while taking this medicine, especially if you have severe or continuing nausea, vomiting, or diarrhea. These conditions may cause you to lose too much water and lead to low blood pressure. You can also loose water by sweating, so drink plenty of water during exercise or in hot weather. Check with your doctor right away if you have bloody urine, a decrease in frequency or amount of urine, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of ...
Rostafuroxin Phase I/II (Hypertension; iv; ouabain antagonist). *Istaroxime Phase I/II (Hearth Failure; oral; inhibition of Na+ ...
Ouabain - A gift from paradise Hauke Furstenwerth Commentary-Cardiovascular Disorders and Medicine (CDM) ...
A ouabain induced depolarization seemed to result from inhibition of an actual electrogenic sodium/potassium pump. Phorbol- ... ouabain; Di-S-C3(5); phorbol myristate acetate; oxygen consumption ...
Ouabain-Na+/K+-ATPase Signaling Regulates Retinal Neuroinflammation and ROS Production Preventing Neuronal Death by an ... The Trophic Effect of Ouabain on Retinal Ganglion Cell is Mediated by EGF Receptor and PKC δ Activation. ... Início The Trophic Effect of Ouabain on Retinal Ganglion Cell is Mediated by EGF Receptor and PKC δ Activation ... Ouabain and BDNF Crosstalk on Ganglion Cell Survival in Mixed Retinal Cell Cultures ...
Effects of insulin, ouabain, and lipolytic agents. Bihler I, Jeanrenaud B. Bihler I, et al. Biochim Biophys Acta. 1970 May 5; ...
The 96-h incubation with 3 nM ouabain or 30 nM MBG elevated the [Na+]i/[K+]i ratio by ~14 and 3-fold and led to differential ... These parameters were not changed after 96-h incubation with 1 nM ouabain or 10 nM MBG. Thus, our results demonstrate that ... Neither [Na+]i/[K+]i ratio nor transcriptome were affected by 6-h incubation with 30 nM ouabain. ... Six hour exposure of HUVEC to 100 and 3,000 nM ouabain resulted in elevation of the [Na+]i/[K+]i ratio by ~15 and 80-fold and ...
Ouabain: A 150-Year-Old Natural Treatment for Heart Disease. Written By. BeWellBuzz ... Ouabain is natures perfect, but forgotten, remedy for heart disease. This post from Foundation for Alternative and Integrative ...
These results suggest hypotensive, cardiomoderating and antioxidant effects of flaxseed in ouabain-induced hypertension in the ... attenuates blood pressure, acetylcholinesterase activity and oxidative stress in ouabain-induced hypertension in normal Wistar ... or 10 µg/kg/day of ouabain diluted in saline solution-treated Oub-Lu or not with 1 per cent of flaxseed (L. usitatissimum) ... redox status markers and acetylcholinesterase enzyme activity in ouabain-induced hypertension in normal Wistar rats. ...
Ouabain decreased both the net reabsorptive rates and the PD. Isosmolal replacement of NaCL by Na-cyclamate (a presumed ...
HGPRT and Ouabain-resistance) in Chinese hamster ovary (CHO) cells, both in the presence and absence of exogenous metabolic ... additional studies were performed at the HGPRT locus and at the Ouabain-resistance marker in these same cells. All studies were ... It was negative at the HGPRT locus and Ouabain-resistance marker. Identical results were obtained with and without metabolic ...
Neuroprotection by Δ9-Tetrahydrocannabinol, the Main Active Compound in Marijuana, against Ouabain-Induced In Vivo ... reduces neuronal injury in neonatal rats injected intracerebrally with the Na+/K+-ATPase inhibitor ouabain to elicit ...
Role of Mn++ in ouabain induced cardiac arrhythmias.. KM Mogre, SS Nayampalli, JJ Bharadwaj, SJ Kashalikar, JB Dharani, SM ...
Publications] Kishimoto,U.et al.: Voltage dependence of the ouabain-sensitive current of the squid axon membrane.In:Cephalopod ... Publications] Kishimoto,U.et al.: Oxford University Press(in press). Voltage dependence of the ouabain-sensitive current of the ...
... and it is inhibited by ouabain. Endothelial cells produce a basement membrane (the Descemet membrane), and they are of ...
Ouabain. approved. unknown. substrate. Details. DB00563. Methotrexate. approved. unknown. substrate. Details. DB00520. ...
Corneal endothelial junctions and the effect of ouabain.. PubMed. 7544491. Feng et al. (1995). The RNA component of human ...
A QUANTITATIVE STUDY OF THE EFFECTS OF OUABAIN UPON THE ELECTROCARDIOGRAM LEONARD APTER, RICHARD ASHMAN and EDGAR HULL ... A QUANTITATIVE STUDY OF THE EFFECTS OF OUABAIN UPON THE ELECTROCARDIOGRAM LEONARD APTER, RICHARD ASHMAN and EDGAR HULL ... A QUANTITATIVE STUDY OF THE EFFECTS OF OUABAIN UPON THE ELECTROCARDIOGRAM LEONARD APTER, RICHARD ASHMAN and EDGAR HULL ...
late blood pressure in ouabain induced hypertensive rats,". Biological & Pharmaceutical Bulletin, vol. 35, no. 12, ...
Chueh S-C, Guh J-H, Chen J, Lai M-K, Teng C-M. Dual effects of ouabain on the regulation of proliferation and apoptosis in ... Ouabain- and marinobufagenin-induced proliferation of human umbilical vein smooth muscle cells and a rat vascular smooth muscle ...
K+-ATPase activity in astrocytes via activation of a distinct subunit highly sensitive to ouabain. J Neurochem 69:2132-2137. ...
"Inversions and adaptation to the plant toxin ouabain shape DNA sequence variation within and between chromosomal inversions of ...
Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. ...
Furthermore, it is possibly also the physiological receptor for endogenous ouabain compounds. ...
Artículo Non-β-blocking carvedilol analog, VK-II-86, prevents ouabain-induced cardiotoxicity ...
Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of ... butyrate has an antimanic effect and protects the brain against oxidative stress in an animal model of mania induced by ouabain ... for butyrates antimanic effect on a rat model of bipolar disorder induced by intracerebroventricular administration of ouabain ...
"Rostafuroxin: An Ouabain Antagonist That Corrects Renal and Vascular Na+-K+-ATPase Alterations in Ouabain and Adducin-Dependent ... Ouabain-infused rats (OS): effect of treatment with 100 μg/kg os Rostafuroxin OS treated Systolic blood Nephrin with Pressure ... Ouabain-infused rats (OS): effect of treatment with methocel (vehicle) Systolic blood Nephrin Pressure Proteinuria optical ... Endogenous Ouabain (EO) has been widely recognized as a new hormone able to control blood pressure through different mechanisms ...
  • Circulating levels of endogenous ouabain (EO), a vasopressor hormone of adrenocortical origin, are increased by sodium depletion. (elsevier.com)
  • Relationships among endogenous ouabain, alpha-adducin polymorphisms and renal sodium handling in primary hypertension. (snpedia.com)
  • Furthermore, it is possibly also the physiological receptor for endogenous ouabain compounds. (multichannelsystems.com)
  • Lanosterol Synthase Genetic Variants, Endogenous Ouabain, and Both Acute and Chronic Kidney Injury. (cdc.gov)
  • This study examines the relative impact of [Na + ] i /[K + ] i -mediated and -independent signaling in transcriptomic changes triggered by the endogenous CTSs ouabain and marinobufagenin (MBG) in human umbilical vein endothelial cells (HUVEC). (nature.com)
  • A ouabain induced depolarization seemed to result from inhibition of an actual electrogenic sodium/potassium pump. (cdc.gov)
  • All experimental solutions contained 100 μM ouabain to block the Na + /K + pump. (elsevier.com)
  • It has been suggested that the interburst hyperpolarization is due to Na+ extrusion by a ouabain-sensitive pump (Johnson et al. (physiomeproject.org)
  • Primary cultures of liver and lung cells from male Sprague Dawley rats were used to metabolically activate the chemicals and the mutation of Chinese Hamster V79 cells to ouabain resistance used to detect mutagenic intermediates. (epa.gov)
  • Burki HJ, Aebersold PM. ( 1978 ) Bromodeoxyuridine-induced mutations in synchronous Chinese hamster cells: temporal induction of 6-thioguanine and ouabain resistance during DNA replication. (academictree.org)
  • Neuroblastoma cells pretreated with ouabain (O) and veratridine (V) in 10 to 1 molar ratio which could be sensitized to VGSC activating toxins. (ncl.edu.tw)
  • Ouabain is nature's perfect, but forgotten, remedy for heart disease. (bewellbuzz.com)
  • Other studies had demonstrated that phosphatidic acid (PA) increases the ouabain-resistant Na + -ATPase activity upon angiotensin II treatment [ 18 ]. (biomedcentral.com)
  • Analysis of the development of high affinity ouabain binding sites and Na+,K+-ATPase activity in the intact pineal gland indicated that the developmental pattern of both resemble the development of ouabain inhibition of the adrenergic stimulation of N-acetyltransferase activity. (nih.gov)
  • These findings indicate ouabain probably has little inhibitory effect on the norepinephrine stimulation of N-acetyltransferase activity in the neonatal because a high affinity ouabain binding form of Na+,K+-ATPase activity, similar to the alpha + form identified in rat brain, is at very low levels in the pinealocyte. (nih.gov)
  • Low concentration of ouabain also induced endocytosis of the Na/K-ATPase and compartmentalization of some signaling molecules (e.g. c-Src, EGFR, and p42/44 MAPKs) into clathrin-coated pits, early and late endosomes. (imrpress.com)
  • Ouabain-induced endocytosis of the Na/K-ATPase depends on the activation of Src kinase, clathrin-coated pits formation, and caveolin-1 (the major component of caveolae). (imrpress.com)
  • The data also show a stronge interplay of ouabain-induced endocytosis of the Na/K-ATPase and signaling transduction. (imrpress.com)
  • Muscle biopsies were taken at rest from the vastus lateralis muscle before and after 7 wk of training and were assayed for Na(+)-K(+)-ATPase concentration using vanadate-facilitated [3H]ouabain binding to intact samples. (nih.gov)
  • To determine the mechanism of nucleotide dependent, Na + stimulated binding of [ 3 H]ouabain to (Na + + K + )-ATPase (EC 3.6.1.3. (uky.edu)
  • In the presence of Na + and Mg ++ , β, γ methylene ATP did not support [ 3 H]ouabain binding to rat brain (Na + + K + )-ATPase and it inhibited ATP dependent binding. (uky.edu)
  • When [ 3 H]ouabain binding to guinea pig kidney (Na + + K + )-ATPase was determined in the presence of Na + , Mg ++ , and Pi, the addition of β, γ methylene ATP was inhibitory, in contrast to the stimulation produced by ATP. (uky.edu)
  • The results show that β, γ methylene ATP binds to the (Na + + K + )-ATPase and that this interaction does not support [ 3 H]ouabain binding. (uky.edu)
  • abstract = "To determine the mechanism of nucleotide dependent, Na+ stimulated binding of [3H]ouabain to (Na+ + K+)-ATPase (EC 3.6.1.3. (uky.edu)
  • However, it induced an additional significant depolarization in these stages when their plasma membrane was already partially depolarized by the H -ATPase inhibitor dicyclohexylcarbo-diimide, indicating the presence of an ouabain-sensitive sodium pump whose activity is masked by the H -ATPase. (bioone.org)
  • Carnosine prevents necrotic and apoptotic death of rat thymocytes via ouabain-sensitive Na/K-ATPase. (nih.gov)
  • It is known that ouabain, a selective inhibitor of Na/K-ATPase, not only can cause the activation of signal cascades, which regulate the cell viability, but also can cause the accumulation of free radicals, which can evoke the oxidative stress. (nih.gov)
  • Chronic Ouabain Prevents Na,K-ATPase Dysfunction and Targets AMPK and IL-6 in Disused Rat Soleus Muscle. (wjgnet.com)
  • After various pretreatments (e.g., removal of endothelium, partial depolarization to −41 mV, blocking of the Na + /Ca 2+ -exchanger (NCX) in reverse mode by KB-R7943, or blocking of the Na + /K + -ATPase by ouabain), the vessels were exposed to ROS. (arvojournals.org)
  • Propagating waves of SD were reliably induced by disrupting the extracellular potassium concentration ([K+]o) either directly or by inhibition of the Na+/K+-ATPase with ouabain. (sdbonline.org)
  • In control glands, bafilomycin-A 1 -sensitive V-ATPase activity and ouabain-sensitive Na + /K + -ATPase activity accounted for 36% and 19%, respectively, of the total ATPase activity. (biologists.com)
  • In human preparations, the HAuCl4 I50 concentration was ouabain insensitive ATPase equally, but gold-sodium-thiomalate inhibited K and Na dependent ATPase 2 to 3 times as effectively as HAuCl4. (cdc.gov)
  • The substitutions Q111T-N122H-F786N-T797A (A-copy mimic) and Q111T-N122H-F786N (B-copy mimic) mediated high insensitivity to ouabain, yet they drastically lowered ATPase activity. (datadryad.org)
  • This effect was phenocopied by treatment of embryos with ouabain, an inhibitor of Na,K-ATPase activity. (zfin.org)
  • Effects of ethanol on ouabain inhibition of mouse brain (Na+,K+)ATPase activity. (ucdenver.edu)
  • Myocardial Na,K-ATPase was quantified in crude homogenates by K-dependent pNPPase activity in rats, and in intact samples by 3 H-ouabain binding in guinea pigs. (regsj.dk)
  • Ouabain binding site in a functioning Na+/K+-ATPase. (nih.gov)
  • Ouabain inhibited 86RbCl uptake by 80% in rabbit gastric superficial epithelial cells (SEC), revealing the presence of a functional Na+,K+-ATPase [(Na+ + K+)-transporting ATPase] pump. (omicsdi.org)
  • Intact SEC were used to study the ouabain-sensitive Na+,K+-ATPase and K+-pNPPase (K+-stimulated p-nitrophenyl phosphatase) activities before and after lysis. (omicsdi.org)
  • The lysed SEC, on the other hand, demonstrated both ouabain-sensitive Na+,K+-ATPase and K+-pNPPase activities. (omicsdi.org)
  • 1. An ATPase (adenosine triphosphatase) preparation obtained from pig brain microsomes by treatment with sodium iodide showed four apparently different ouabain-sensitive activities under various conditions. (omicsdi.org)
  • They were (a) ouabain-sensitive Mg(2+)-stimulated ATPase, (b) K(+)-stimulated ATPase, (c) (Na(+),K(+))-stimulated ATPase and (d) Na(+)-stimulated ATPase activities. (omicsdi.org)
  • The concentration producing 50% inhibition was 0.1mum for ouabain-sensitive Mg(2+)-stimulated ATPase, 0.2mum for K(+)-stimulated ATPase, 0.1mum for (Na(+),K(+))-stimulated ATPase and 0.003mum for Na(+)-stimulated ATPase activity. (omicsdi.org)
  • 4. The ouabain-sensitive ATPase activities were inactivated by N-ethylmaleimide but the insensitive ATPase activity was not. (omicsdi.org)
  • 5. The three ouabain-sensitive ATPase activities were inhibited about 50% by 1mm-Ca(2+), whereas the ouabain-sensitive Mg(2+)-stimulated ATPase activity was activated by the same concentration of Ca(2+). (omicsdi.org)
  • Inhibitors from the Na+-K+ ATPase pump, for instance, the cardiac glycoside ouabain, have already been shown to decrease CSF creation and the motion of Na+ in to the CSF [12]. (technigraphicscorp.com)
  • The increase in [3H]ouabain binding sites was prevented by the addition of myo-inositol (10 mM), by inhibition of the protein kinase C with staurosporine (100 nM) and by inhibition of the Na/H antiport with dimethylamiloride (50 microM). (ox.ac.uk)
  • However, appreciable K+-pNPPase activity sensitive to ouabain inhibition was demonstrated by localizing its activity to the cell-surface exterior. (omicsdi.org)
  • Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery. (biomedfrontiers.org)
  • Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. (biomedfrontiers.org)
  • Endogenous Ouabain (EO): a new biomarker of subclinical cardiovascular damage. (biomedfrontiers.org)
  • Endogenous Ouabain (EO) is a neuroendocrine hormone synthesized in the adrenal cortex 1-3 . (biomedfrontiers.org)
  • Endogenous cardiotonic steroids (CTS), and in particular Endogenous Ouabain, are implicated in regulation of natriuresis and vascular tone 11 . (biomedfrontiers.org)
  • Recently, we reported few significant associations between pre-operative Endogenous Ouabain levels and adverse renal outcomes and higher mortality rate in cardiac surgery patients and in critically ill ones 14-16 . (biomedfrontiers.org)
  • El-Mallakh RS , Gao Y , You P . Role of endogenous ouabain in the etiology of bipolar disorder. (wjgnet.com)
  • DLIS but not endogenous ouabain concentrations were found to be related to left ventricular function. (labome.org)
  • Steroid biosynthesis and renal excretion in human essential hypertension: association with blood pressure and endogenous ouabain. (cdc.gov)
  • Pathways of excretion of the rapidly acting cardiac glycoside ouabain were studied in dogs and human subjects by means of a recently developed radioimmunoassay method and also by recovery of 3 H counts after 3 H-ouabain administration. (aspetjournals.org)
  • This study compared the positive inotropic actions of milrinone in isolated rabbit myocardium with that of the conventional positive inotropic drug, dobutamine, and a cardiac glycoside, ouabain. (elsevier.com)
  • In spite of its antitumor potential, the overall biological activity of (+)-strebloside must be regarded as being typical of better-known cardiac glycosides such as digoxin and ouabain. (semanticscholar.org)
  • First, we would like to clarify the roles of digoxin and ouabain in this study. (bmj.com)
  • For instance, there is no difference in the osteophyte number between digoxin and ouabain treatment groups (Figure 2F and 2G). (bmj.com)
  • Having said that, we do appreciate the comments that combined use of digoxin and ouabain with lower dosages of drugs may exert synergistic protective effects against OA and may reduce their side effects, which worthwhile further investigations in future. (bmj.com)
  • All urine, bile and, or feces were collected for at least 4 days in dogs (ouabain plasma concentration half-life of 18 hours) and 5 days in humans (ouabain plasma concentration half-life of 22 hours) after ouabain infusion. (aspetjournals.org)
  • Moreover, low concentration ouabain significantly reduced transcellular Na + transport. (imrpress.com)
  • The muscle [3H]ouabain binding site concentration was significantly increased (16%) from 333 +/- 19 to 387 +/- 15 (SE) pmol/g wet wt after training but was unchanged in muscle obtained from three control subjects. (nih.gov)
  • The increased muscle [3H]ouabain binding site concentration and the reduced ratio of rise in [K+] relative to work output with exercise are both consistent with improved plasma and skeletal muscle K+ regulation after sprint training. (nih.gov)
  • We have shown that the nanomolar concentrations of ouabain result in the temporary increase in the level of intracellular free radicals, but the millimolar concentration of ouabain induces a stable intracellular accumulation of free radicals in rat thymocytes. (nih.gov)
  • 4. The concentration of Na + , K + -pumps was quantified as the total capacity for [ 3 H]ouabain binding. (portlandpress.com)
  • L-NAME, charybdotoxin + apamin, KCl, and ouabain shifted the bradykinin concentration-response curve (CRC) ≈10-fold to the right BaCl2 did not exert additional effects on top of ouabain. (eur.nl)
  • 3. These activities were inhibited by low concentration of ouabain. (omicsdi.org)
  • Lithium (1-8 mM) caused a dose-dependent increase in the number of [3H]ouabain binding sites and in sodium/potassium (Na/K) pump activity in normal lymphocytes after incubation for 72 h. (ox.ac.uk)
  • Similarly, ouabain (1 nM to 1 mM) had no effect on 86Rb uptake in the 2-day-old gland but blocked (IC50 congruent to 20 nM) 86Rb uptake in the adult gland. (nih.gov)
  • Ouabain and bumetanide, an inhibitor of the Na + /K + /Cl − cotransporter, each inhibited Rb + uptake maximally by 66 and 30%, respectively. (unthsc.edu)
  • In functional expression studies in Xenopus laevis oocytes, oatp2 mediated uptake of the bile acids taurocholate (Km approximately 35 microM) and cholate (Km approximately 46 microM), the estrogen conjugates 17beta-estradiol-glucuronide (Km approximately 3 microM) and estrone-3-sulfate (Km approximately 11 microM), and the cardiac gylcosides ouabain (Km approximately 470 microM) and digoxin (Km approximately 0.24 microM). (unibas.ch)
  • The aim of this study was to evaluate the effect of inhibitors such as ouabain, reserpine and verapamil in the killing activity of macrophages infected with Mycobacterium tuberculosis. (unl.pt)
  • Activities of both ATPases were probed in salivary gland homogenates by applying specific inhibitors for these ion pumps, namely ouabain and bafilomycin A 1 . (biologists.com)
  • 6. Ouabain Modulates the Adherens Junction in Renal Epithelial Cells. (nih.gov)
  • 0.001) reduced by 100-fold to 1.6 x 10 -7 M. Thus, milrinone is significantly less potent than dobutamine or ouabain in vitro and is without contractile effect at clinically relevant concentrations. (elsevier.com)
  • Thus, milrinone is significantly less potent than dobutamine or ouabain in vitro and is without contractile effect at clinically relevant concentrations. (elsevier.com)
  • The increasing level of free radicals resulting from both low and high concentrations of ouabain can be attenuated by the antioxidant, carnosine. (nih.gov)
  • 5. Comparison of the concentrations of K + , Mg 2+ and [ 3 H]ouabain-binding sites in samples obtained post mortem showed modest variation among different muscles with varying fibre composition. (portlandpress.com)
  • Ouabain binding was irreversible, and, as in erythrocytes, was inhibited by K. At external concentrations of 0.1 mM, influxes of lysine and leucine were entirely carrier-mediated, with means of 0.021 nmol/10 6 cells x min, and 0.019 nmol/10 6 cells x min, respectively. (rupress.org)
  • mutations or translocations seldom recurred in-field, Ouabain IC50 whereas the ones that lacked such mutations or harbored mutations had been more likely to see in-field recurrence (14). (calcipotriol.net)
  • We, as a result, identified Ouabain IC50 melanoma sufferers treated with SRS at our organization and examined their outcomes predicated on mutation position. (calcipotriol.net)
  • Evaluations had been finished with the Ouabain IC50 log-rank-test. (calcipotriol.net)
  • Second, LC was approximated with KaplanCMeier curves and weighed against a FrailtyCCox Ouabain IC50 model accounting for within-cluster relationship by incorporating cluster results as impartial and identically distributed arbitrary factors (22). (calcipotriol.net)
  • it was found that K+ (80 microM) inhibited the adrenergic stimulation of N-acetyltransferase activity at all ages but that ouabain (1 nM to 1 mM) treatment was not inhibitory early in development. (nih.gov)
  • Ouabain effects on activated lymphocytes: augmentation of CD25 expression on TPA-stimulated cells and of CD69 on PHA-and TPA-stimulated cells. (nih.gov)
  • Ouabain inhibitor rostafuroxin attenuates dextromethorphan-induced manic potential. (wjgnet.com)
  • Rostafuroxin (PST-2238) is an ouabain-inhibitor counteracting specific forms of hypertension. (adooq.com)
  • Lastly, flies with low levels of protein kinase G (PKG) had increased latencies to onset of both ouabain-induced SD and anoxic depolarization compared to flies with higher levels. (sdbonline.org)
  • Moreover, the long-term incubation with ouabain leads to the cell death by necrosis and apoptosis. (nih.gov)
  • Subjecting horse spermatozoa to hypoosmotic incubation: effects of ouabain. (ufps.edu.co)
  • Ouabain-activated signaling pathways lead to the induction of some early response proto-oncogenes, activation of transcription factors, and cardiac hypertrophy. (imrpress.com)
  • Along with these observations, Dr Mesquita also found that since the beginning of the twentieth century, several doctors had used cardiotonics (cardiac glycosides like digoxin, digitoxin, and ouabain / strophanthin), with remarkable results in the treatment of both stable angina pectoris and acute myocardial infarction. (positivehealth.com)
  • Lynch, RM & Paul, RJ 1982, ' Metabolic compartmentalization in vascular smooth muscle (VSM): Effect of ouabain on glucose transport and catabolism ', Federation Proceedings , vol. 41, no. 4, pp. 4173. (arizona.edu)
  • The molecular structure of ouabain consists of rhamnoside (a common glycone component of glycosides) and ouabagenin (a highly oxygenated steroid). (ku.dk)
  • Cardiac glycosides (including ouabain and marinobufagin, MBG) are a new class of steroid hormones. (imrpress.com)
  • Phenolphthalein induced chromosomal aberrations, Hprt gene mutations and morphological transformation but not aneuploidy or ouabain-resistant mutations or sister chromatid exchange in cultured mammalian cells. (inchem.org)
  • At the physiological resting membrane potential, ROS exposure led to a significant vasodilatation, which was significantly reduced by pretreatment with ouabain. (arvojournals.org)
  • Male Wistar rats were treated with ouabain (~8.0 µg/day, subcutaneously) or vehicle for 5 and 20 weeks, and spontaneously hypertensive rats (SHRs) for 5 weeks. (utoledo.edu)
  • Aortas from 20-week ouabain-treated Wistar rats showed reduced COX-2 and enhanced eNOS protein expression. (utoledo.edu)
  • In contrast, ouabain had no effect on the ΔΨ of the procyclic stages in a sodium-rich buffer. (bioone.org)
  • May participate in the regulation of membrane transport of ouabain. (nih.gov)
  • However, digoxin also showed significant protective effects against OA in multiple analyses performed, quite similar to ouabain. (bmj.com)
  • Both ouabain and digoxin are FDA-approved drugs and their side effects have been well established. (bmj.com)
  • Thus, while renal excretion is the predominant route of ouabain elimination, gastrointestional excretion is also substantial in both dog and man. (aspetjournals.org)
  • Despite its high toxicity, the environmental occcurence of ouabain as well as its interactions with the surrounding environment is barely reported, rendering it a promising candidate for further study. (ku.dk)
  • In addition, both ouabain and digoxin did not show detectable toxicity in our in vitro and in vivo assays (online supplemental figure 11). (bmj.com)
  • In contrast, in the neonate, ouabain (1-100 nM) enhanced adrenergic induction of N-acetyltransferase activity, and ouabain treatment alone (1-1000 nM) stimulated N-acetyltransferase activity. (nih.gov)
  • In SHRs, 5-week ouabain treatment reduced COX-2 and increased nNOS protein expression. (utoledo.edu)
  • The True Cause of Heart Attacks explores the true cause of heart attacks and angina, along with the the use of carditonics, in particular ouabain, in the treatment of cardiac disease. (fleetwoodonsite.com)
  • Na+ is shown to be the sole charge carrier as the short circuit current is inhibited reversibly by fetal applications of amiloride and replacement of Na+ by choline in the Ringer solution, and irreversibly by both fetal and maternal applications of ouabain. (ed.ac.uk)
  • Therefore, we chose both ouabain and digoxin as the representatives of cardenolides in this study and emphasized the potential importance of digoxin in treating patients with OA in clinics. (bmj.com)
  • Among four dogs, after single i.v. doses of 3 H-ouabain, urinary excretion of 3 H counts averaged 54 ± 2.3% of the i.v. dose. (aspetjournals.org)
  • The two main purposes of this study were to evaluate the survival of mouse MSCs transplanted into normal and ouabain-treated gerbil cochleae and to determine the migratory patterns of MSCs with two differing injection methods. (northwestern.edu)
  • With the scala tympani injection, there were no profiles found in the modiolus either in the control or ouabain-treated cochleae. (northwestern.edu)
  • RESULTS: Our findings indicated that undifferentiated MSCs were able to survive in the modiolus both in the control and the ouabain-treated cochleae. (northwestern.edu)
  • DESIGN: The animals were deafened by ouabain, which damaged SGNs while leaving hair cell systems intact. (northwestern.edu)
  • The average number of profiles found in the modiolus was greater in the ouabain-treated cochleae than in the control cochleae. (northwestern.edu)