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Chemical Compound Review

Ouabaine     4-[1,5,11,14-tetrahydroxy- 10...

Synonyms: Strophanthin G, AGN-PC-00AX0E, NSC-25485, AC1L1IJG, AC1Q6AXD, ...
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Disease relevance of Acocantherin

  • We have found that cultured fibroblasts from patients with cystic fibrosis (CF) accumulate less 22Na in the presence of ouabain than do normal cells [1].
  • We measured the ability of plasma extracts from patients with acromegaly to inhibit the binding of ouabain to the sodium pump in normal red cells and to inhibit the enzymatic activity (sodium-potassium-ATPase) of the sodium pump in membrane preparations from normal kidneys [2].
  • Induction of erythroid differentiation in ouabain-resistant murine erythroleukemia cells by ouabain is reported [3].
  • This strategy has been used here to stabilize cardiac arrhythmias induced by the drug ouabain in rabbit ventricle [4].
  • Concentrations of ouabain used ranged from 3.3 x 10(-10) molar to 5 x 10(-7) molar and produced an increased force of contraction without any evidence of toxicity [5].

Psychiatry related information on Acocantherin

  • It is concluded that the inotropic effect of ouabain is negligible during strenuous physical activity because of the presence of high levels of sympathetic stimulation [6].
  • Red cell ouabain-sensitive Na+-K+-adenosine triphosphatase: a state marker in affective disorder inversely related to plasma cortisol [7].
  • Ouabain binding in the human brain. Effects of Alzheimer's disease and aging [8].
  • 4. Intrinsic CNS activity during REM sleep may be involved in the centrally mediated arrhythmogenic properties of ouabain during sleep [9].
  • Additional experiments were done in which we superfused PF from adult and old animals with O for long periods to determine the time-response relationships for ouabain effects on maximum diastolic potential, action potential amplitude, Vmax and APD50 [10].

High impact information on Acocantherin

  • Pituitary adenomectomy decreased plasma volume and the inhibition by plasma of ouabain binding [2].
  • Restoration by KCl was blocked by ouabain, indicating that uptake via the Na+/K+ ATPase was required [11].
  • After equilibration with 22Na in ouabain-exposed cells to that in unexposed cells, after five hours of incubation, was 2.34 +/- 0.14 (mean +/- S.D.) in 13 fibroblast strains from normal subjects and 1.33 +/- 0.08 in eight strains from patients with CF [1].
  • The hybrids formed between near-diploid parental cells resembled Friend cells in the ability to grow in suspension and to synthesize hemoglobin in the presence of the chemical inducers dimethyl sulfoxide (DMSO) and ouabain [12].
  • These results suggest that the binding of ouabain to the plasma membrane enzyme, Na/K ATPase, is required for the induction of erythroid differentiation by ouabain [3].

Chemical compound and disease context of Acocantherin


Biological context of Acocantherin


Anatomical context of Acocantherin


Associations of Acocantherin with other chemical compounds


Gene context of Acocantherin

  • HRAS-transformed FE-8 cells showed an increased sensitivity toward ouabain when compared to their normal counterparts [32].
  • Incubation of HSMC with 100 nM ouabain increased phosphorylation of the alpha-subunits of the Na-pump at a MAPK-specific Thr-Pro motif [33].
  • Here, we explored the roles of Src and the EGFR in the ouabain-invoked pathways that lead to the activation of MAPKs [34].
  • The aim of this work was to examine the ouabain-induced events upstream of the Ras/MAPK cascade [35].
  • These data, in conjunction with our previous findings on the signaling role of Na+/K+-ATPase in other cells, suggest that ouabain-induced activation/transactivation of Src/EGFR by Na+/K+-ATPase leads to activation of ERK1/2, the resulting increase in the level of cell cycle inhibitor p21Cip1, and growth arrest [36].

Analytical, diagnostic and therapeutic context of Acocantherin

  • CA2+-free perfusion of rat heart reveals a (Na+ + K+)ATPase form highly sensitive to ouabain [37].
  • Regional blood flow alterations during occlusion and reperfusion were simultaneously determined utilizing 15 mum radioactive microspheres to determine the degree to which altered binding of ouabain might be flow related [38].
  • Using the inhibition of ouabain-insensitive sodium transport in erythrocytes as an assay to identify the factor, we ran the crude promyelocyte extract through Sephadex G-25 and G-10, with an intermediate ion-exchange step on DE-32, and finally subjected the active fraction to reverse-phase high-performance liquid chromatography [39].
  • Microinjection of ouabain into the unilateral RVLM of anesthetized normotensive rats elicited dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) [40].
  • To investigate the mechanism responsible for this change, we compared the maximal Na-K-ATPase hydrolytic activity, the ouabain sensitive 86Rb influx, the specific [3H]ouabain binding, and the sensitivity of Na-K-ATPase to ouabain in the CCD of control rats and of rats given an intraperitoneal injection of puromycin 7 d before study [41].


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  3. Induction by ouabain of hemoglobin synthesis in cultured Friend erythroleukemic cells. Bernstein, A., Hunt, D.M., Crichley, V., Mak, T.W. Cell (1976) [Pubmed]
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  11. Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts. Larkin, J.M., Brown, M.S., Goldstein, J.L., Anderson, R.G. Cell (1983) [Pubmed]
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  16. Effects of amrinone on contraction and K+-induced contracture of normal and subacutely failed cat ventricular muscle. Gaide, M.S., Kimura, S., Lodge, N.J., Cameron, J.S., Kozlovskis, P.L., Myerburg, R.J., Bassett, A.L. Circulation (1986) [Pubmed]
  17. Binding sites related to ouabain-induced stimulation or inhibition of the sodium pump. Godfraind, T., Ghysel-Burton, J. Nature (1977) [Pubmed]
  18. Salt-sensitive hypertension is triggered by Ca2+ entry via Na+/Ca2+ exchanger type-1 in vascular smooth muscle. Iwamoto, T., Kita, S., Zhang, J., Blaustein, M.P., Arai, Y., Yoshida, S., Wakimoto, K., Komuro, I., Katsuragi, T. Nat. Med. (2004) [Pubmed]
  19. Ouabain-like activity in toad skin and its implications for endogenous regulation of ion transport. Flier, J.S. Nature (1978) [Pubmed]
  20. Amino-acid sequence of the catalytic subunit of the (Na+ + K+)ATPase deduced from a complementary DNA. Shull, G.E., Schwartz, A., Lingrel, J.B. Nature (1985) [Pubmed]
  21. Amiloride directly inhibits the Na,K-ATPase activity of rabbit kidney proximal tubules. Soltoff, S.P., Mandel, L.J. Science (1983) [Pubmed]
  22. Endogenous ouabain-like compound increases heart muscle contractility. Shimoni, Y., Gotsman, M., Deutsch, J., Kachalsky, S., Lichtstein, D. Nature (1984) [Pubmed]
  23. K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Edwards, G., Dora, K.A., Gardener, M.J., Garland, C.J., Weston, A.H. Nature (1998) [Pubmed]
  24. External Na dependence of ouabain-sensitive ATP:ADP exchange initiated by photolysis of intracellular caged-ATP in human red cell ghosts. Kaplan, J.H., Hollis, R.J. Nature (1980) [Pubmed]
  25. Selective extraction of small and large molecules from the cerebrospinal fluid by Purkinje neurons. Borges, L.F., Elliott, P.J., Gill, R., Iversen, S.D., Iversen, L.L. Science (1985) [Pubmed]
  26. Retroviral vector-mediated gene transfer into human hematopoietic progenitor cells. Gruber, H.E., Finley, K.D., Hershberg, R.M., Katzman, S.S., Laikind, P.K., Seegmiller, J.E., Friedmann, T., Yee, J.K., Jolly, D.J. Science (1985) [Pubmed]
  27. Ouabain stimulation of noradrenaline transport in guinea pig heart. Sharma, V.K., Pottick, L.A., Banerjee, S.P. Nature (1980) [Pubmed]
  28. Imaging elemental distribution and ion transport in cultured cells with ion microscopy. Chandra, S., Morrison, G.H. Science (1985) [Pubmed]
  29. Ouabain resistance conferred by expression of the cDNA for a murine Na+, K+-ATPase alpha subunit. Kent, R.B., Emanuel, J.R., Ben Neriah, Y., Levenson, R., Housman, D.E. Science (1987) [Pubmed]
  30. Transport defects of rabbit medullary thick ascending limb cells in obstructive nephropathy. Hwang, S.J., Haas, M., Harris, H.W., Silva, P., Yalla, S., Sullivan, M.R., Otuechere, G., Kashgarian, M., Zeidel, M.L. J. Clin. Invest. (1993) [Pubmed]
  31. Src activation generates reactive oxygen species and impairs metabolism-secretion coupling in diabetic Goto-Kakizaki and ouabain-treated rat pancreatic islets. Kominato, R., Fujimoto, S., Mukai, E., Nakamura, Y., Nabe, K., Shimodahira, M., Nishi, Y., Funakoshi, S., Seino, Y., Inagaki, N. Diabetologia (2008) [Pubmed]
  32. Partial reversion of the transformed phenotype in HRAS-transfected tumorigenic cells by transfer of a human gene. Schaefer, R., Iyer, J., Iten, E., Nirkko, A.C. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  33. Cardiotonic steroids stimulate glycogen synthesis in human skeletal muscle cells via a Src- and ERK1/2-dependent mechanism. Kotova, O., Al-Khalili, L., Talia, S., Hooke, C., Fedorova, O.V., Bagrov, A.Y., Chibalin, A.V. J. Biol. Chem. (2006) [Pubmed]
  34. Src-mediated inter-receptor cross-talk between the Na+/K+-ATPase and the epidermal growth factor receptor relays the signal from ouabain to mitogen-activated protein kinases. Haas, M., Wang, H., Tian, J., Xie, Z. J. Biol. Chem. (2002) [Pubmed]
  35. Involvement of Src and epidermal growth factor receptor in the signal-transducing function of Na+/K+-ATPase. Haas, M., Askari, A., Xie, Z. J. Biol. Chem. (2000) [Pubmed]
  36. Digitalis-induced signaling by Na+/K+-ATPase in human breast cancer cells. Kometiani, P., Liu, L., Askari, A. Mol. Pharmacol. (2005) [Pubmed]
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  38. Ischemia-induced alterations in myocardial (Na+ + K+)-ATPase and cardiac glycoside binding. Beller, G.A., Conroy, J., Smith, T.W. J. Clin. Invest. (1976) [Pubmed]
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  41. Mechanism of enhanced Na-K-ATPase activity in cortical collecting duct from rats with nephrotic syndrome. Féraille, E., Vogt, B., Rousselot, M., Barlet-Bas, C., Cheval, L., Doucet, A., Favre, H. J. Clin. Invest. (1993) [Pubmed]
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