Disease relevance of ouabain

• The effects of ischemia on the canine myocardial (Na+ + K+)-ATPase complex were examined in terms of alterations in cardiac glycoside binding and enzymatic activity [1].
• Both heterologous IgG and Fab fragments of appropriate affinity and specificity have been shown capable of reversing advanced cardiac glycoside toxicity [2].
• The sodium pump and hypertension: a physiological role for the cardiac glycoside binding site of the Na,K-ATPase [3].
• Modulation of cytokine production and protection against lethal endotoxemia by the cardiac glycoside ouabain [4].
• Effects of a cardiac glycoside on regional function, blood flow, and electrograms in conscious dogs with myocardial ischemia [5].

Psychiatry related information on ouabain

• Cardiac glycoside toxicity. An unusual manifestation of drug addiction [6].

High impact information on ouabain

• Na,K-ATPase beta2 expression is negligible, indicating that the human cardiac glycoside receptors are alpha1beta1, alpha2beta1, and alpha3beta1. alpha3, beta1, sodium pump activity, and Na+-Ca++ exchanger levels were 30-50% lower in atria compared to ventricles and/or septum; differences between ventricles and septum were insignificant [7].
• Thyroid-induced alterations in myocardial sodium-potassium-activated adenosine triphosphatase, monovalent cation active transport, and cardiac glycoside binding [8].
• We conclude that reduced regional myocardial blood flow, local alterations in cellular milieu, and altered glycoside-binding properties of (Na+ + K+)-ATPase all participate in the reduction of cardiac glycoside binding observed after reperfusion of ischemic myocardium [1].
• BACKGROUND: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing [9].
• Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-alpha/NF-kappaB signaling pathway [10].

Chemical compound and disease context of ouabain

• Digoxin was administered to normal CD-1 mice (4 micrograms/kg per 24 hr), and the mice were inoculated intratracheally with Streptococcus pneumoniae in order to assess the effects of the cardiac glycoside on pulmonary antibacterial mechanisms [11].
• Digitoxin should therefore be the cardiac glycoside of choice in treatment of patients with renal failure [12].
• Investigation of electrophysiologic mechanisms for the antiarrhythmic actions of R 56865 in cardiac glycoside toxicity [13].
• Twelve patients with severe chronic congestive heart failure (CHF) received prazosin in a dose of 4 to 20 mg daily for a period of 2 months, in addition to cardiac glycoside and diuretic drugs [14].
• In 12 patients with severe congestive heart failure (CHF), captopril in doses of 25 to 150 mg, every 8 hours, was given for a period of 2 months, in addition to cardiac glycoside and diuretic drugs [15].

Biological context of ouabain

• The highly conserved cardiac glycoside binding site of Na,K-ATPase plays a role in blood pressure regulation [16].
• In the brain of the rat, high- and low-affinity cardiac glycoside receptors have been shown to be associated with two structurally different isoforms of the catalytic subunit of the Na+,K+-ATPase, termed alpha and alpha(+) [17].
• Cardiac glycoside sensitivity can evidently be regulated at the level of gene expression by developmental signals [17].
• Förster energy transfer between cardiac glycoside binding sites labeled with anthroylouabain and fluoresceinylethylenediamino ouabain gave a distance of 4.9 +/- 0.5 nm [18].
• These experiments demonstrate that this chimera behaves as a functional ion pump and indicate that the protein domains involved in cardiac glycoside binding are not confined to the amino-terminal half of the Na,K-ATPase [19].

Anatomical context of ouabain

• To determine contributory mechanisms for the effects of PROT on myocyte sarcolemmal systems, beta-receptor- and cardiac glycoside-binding characteristics were determined in sarcolemmal preparations. beta-receptor binding was 175 +/- 10 fmol/mg and was reduced to 140 +/- 6 fmol/mg in the presence of PROT (P < .05) [20].
• The effects of the cardiac glycoside ouabain and an "ouabain-like compound" (OLC), which was extracted and partially purified from sheep brain, were contrasted using both the resting and hyperpolarized fibroblasts [21].
• Intracellular sodium and the positive inotropic effect of veratridine and cardiac glycoside in sheep Purkinje fibers [22].
• The role of arterial baroreceptors in mediating the cardiovascular response to a cardiac glycoside in conscious dogs [23].
• Biochemical and cross-resistance studies with HeLa cell mutants resistant to cardiac glycoside SC4453. Regulation of the resistant form of Na+/K+-ATPase in the mutant cells [24].

Associations of ouabain with other chemical compounds

• Digoxin-like immunoreactive factor (DLIF) from adrenal cortex is an endogenous molecule with structural features remarkably similar to those of digoxin, a plant-derived cardiac glycoside (Shaikh, I. M., Lau, B. W. C., Siegfried, B. A., and Valdes, R., Jr. (1991) J. Biol. Chem. 266, 13672-13678) [25].
• Digoxin, the cardiac glycoside most frequently used in clinical practice in the United States, can be given orally or intravenously and has an excretory half-life of 36 to 48 hours in patients with serum creatinine and blood urea nitrogen values in the normal range [26].
• Erythrosin B inhibits high affinity ouabain binding in guinea-pig heart Na+-K+-ATPase without influence on cardiac glycoside induced contractility [27].
• This study describes the effects of the cardiac glycoside analogue strophanthidin on spontaneous action potentials and L-type calcium current recorded from single AVN cells isolated from the rabbit heart [28].
• Effects of quinidine on the cardiac-glycoside sensitivity of guinea-pig and rat heart [29].

Gene context of ouabain

• Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-kappaB and AP-1 modulator [30].
• This result indicates that the cardiac glycoside binding site of the alpha1 isoform can also mediate ACTH-induced hypertension [16].
• FGF-2 secretion from HEK 293 or CV-1 cells was linear over time and sensitive to inhibition by the cardiac glycoside ouabain, a specific inhibitor of the Na,K-ATPase [31].
• Cardiac glycoside inhibits IL-8-induced biological responses by downregulating IL-8 receptors through altering membrane fluidity [32].
• The Oatp2-specific cardiac glycoside digoxin, however, is not transported [33].

Analytical, diagnostic and therapeutic context of ouabain

• Development of a hypothetical transmembrane organization for the alpha subunit and application of site-specific mutagenesis techniques have allowed significant progress to be made toward identifying amino acids involved in cardiac glycoside resistance and possibly binding [34].
• Methodologic progress and availability of commercial radioimmunoassay kits have placed measurement of clinically relevant serum or plasma cardiac glycoside concentrations within the capability of most well equipped clinical laboratories [35].
• Because of the competitive nature of the immunoassay as well as the complexity of the mixture of cross-reacting cardiac glycosides present in the plant material, the measured apparent digoxin concentration is not linearly related to the cardiac glycoside concentration [36].
• Cardiac glycoside binding to microsomes prepared from rat heart ventricles and enriched in (Na+ + K+)-ATPase was measured by a rapid filtration technique [37].
• Renal tubular transport of a polar cardiac glycoside, ASI-222, in rats; clearance and micropuncture studies [38].

References