Ouabain
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Ouabain is the familiar name of g-strophanthin, a poisonous cardiac glycoside. Ouabain is found in the ripe seeds of African plants Strophanthus gratus and Acokanthera ouabaio. K-strophanthin is found in the ripe seeds of Strophanthus kombé.
Ouabain blocks the Na+/K+-ATPase in higher concentrations which are attainable in vitro or with intravenous dosage. This is the original use of ouabain; digoxin is a generally more popular compound used for similar indications (atrial fibrillation and congestive heart failure).
A recent concept is that at low concentrations ouabain in fact has the opposite effect, namely stimulation of the Na-K-ATPase.[1] This property is not exhibited by digoxin.[2]
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[edit] Endogenous ouabain and ouabain mimics
In 1991 an isomer of ouabain was identified as an endogenous hormone (Hamlyn et al. 1991 & 2003), which is synthesized in the adrenal gland and possibly in the hypothalamus. Its exact mode of action and physiological significance is not yet determined. In normal human plasma, circulating levels ranging from 9 - 600 picoMol ouabain have been found, with higher levels in congestive heart failure, essential hypertension and some cancers. It has been suggested that very low concentrations of ouabain may stimulate the Na+/K+-ATPase while the higher levels achieved during therapy or in pathophysiological disorders may inhibit the NaK-pump.[1]
In the years following the discovery of ouabain in the human circulation, it was found in the adrenal glands of cows (Schneider et al. 1998) and dogs (Boulanger et al. 1993). The putative "isomer" of ouabain found in the hypothalamus was shown subsequently to be ouabain. Earlier hints of an isomer for the brain compound were complicated in part by formation of ouabain-borate complexes due to storage in borosilicate glassware (Kawamura et al. 1999).
[edit] Uses
Ouabain is used worldwide extensively by scientists for in-vitro-studies to block the sodium pump (Na-K-ATPase). In many non rodent species, low concentrations of this substance (i.e., in the nanomolar range) provide effective inhibition of the NaK-pump. The issue in rodents is more complicated because there are different isoforms of the NaK-pump - some of which are very sensitive to ouabain while others are not. Ouabain is no longer widely used for the treatment of human heart failure. However, in France and Germany, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use by mouth in angina pectoris and myocardial infarction. There is limited anecdotal evidence for improved efficacy of ouabain relative to digoxin in a small number of patients. However, no well controlled research exists that proves or disproves the efficacy this practice.
[edit] References
- ^ Gao, J. et al. (2002): Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol 119:297-312. PMID 11929882 PDF
- ^ Saunders, R. & Scheiner-Bobis, G. (2004): Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem 271:1054-62. PMID 15009217 PDF
- Boulanger, B. R.; M. P. Lilly, J. M. Hamlyn, J. Laredo, D. Shurtleff and D. S. Gann (March 1993). "Ouabain is secreted by the adrenal gland in awake dogs". The American Journal of Physiology: Endocrinology and Metabolism 264 (3): E413-E419. PubMed.
- Hamlyn, JM; MP Blaustein, S Bova, DW DuCharme, DW Harris, F Mandel, WR Mathews, JH Ludens (July 1991). "Identification and characterization of an ouabain-like compound from human plasma". Proceedings of the National Academy of Sciences of the United States of America 88 (14): 6259-63. PubMed.
- Kawamura, Akira; Jinsong Guo, Yasuhiro Itagaki, Charles Belldagger, Yi Wangdagger, Garner T. Haupert Jr., Sheila MagilDagger, Rex T. Gallagher, Nina Berova, and Koji Nakanishi (June 8, 1999). "On the structure of endogenous ouabain". Proceedings of the National Academy of Sciences of the United States of America 96 (12): 6654-6659. PubMed.
- Schneider, Ralf; Victor Wray, Manfred Nimtz, Wolf Dieter Lehmannpar , Ulrike Kirch, Roberto Antolovic, and Wilhelm Schoner (January 9, 1998). "Bovine Adrenals Contain, in Addition to Ouabain, a Second Inhibitor of the Sodium Pump". The Journal of Biological Chemistry 273 (2): 784-92. PubMed.
[edit] External links
- [1] Ouabainomics by Hamlyn
| Major Families of Biochemicals | ||
| Peptides | Amino acids | Nucleic acids | Carbohydrates | Lipids | Terpenes | Carotenoids | Tetrapyrroles | Enzyme cofactors | Steroids | Flavonoids | Alkaloids | Polyketides | Glycosides | ||
| Analogues of nucleic acids: | Types of Glycosides | Analogues of nucleic acids: |
| Bond: | O-glycosidic bond | S-glycosidic bond | N-glycosidic bond | |
|---|---|---|
| Geometry: | α-Glycoside | β-Glycoside | 1,4-Glycoside | 1,6-Glycoside | |
| Glycone: | Glucoside | Fructoside | Glucuronide | |
| Aglycone: | Alcoholic glycoside | Anthraquinone glycoside | Coumarin glycoside | Cyanogenic glycoside | Flavonoid glycoside | Phenolic glycoside | Saponin | Cardiac glycoside | Steviol glycoside | Thioglycoside | Glycosylamine | Bufanolide | Cardenolide | |
