Journal article
Selectivity of Digitalis Glycosides for Isoforms of Human Na,K-ATPase
Journal of Biological Chemistry, Vol.285(25), pp.19582-19592
Jun/2010
Abstract
There are four isoforms of the alpha subunit (alpha 1-4) and three isoforms of the beta subunit (beta 1-3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. alpha 2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An alpha 2-selective cardiac glycoside could provide important insights into physiological and pharmacological properties of alpha 2. The isoform selectivity of a large number of cardiac glycosides has been assessed utilizing alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 isoforms of human Na, K-ATPase expressed in Pichia pastoris and the purified detergent-soluble isoform proteins. Binding affinities of the digitalis glycosides, digoxin, beta-methyl digoxin, and digitoxin show moderate but highly significant selectivity (up to 4-fold) for alpha 2/beta 3 over alpha 1 (K(D) alpha 1 > alpha 2 = alpha 3). By contrast, ouabain shows moderate selectivity (approximate to 2.5-fold) for alpha 1 over alpha 2 (K(D) alpha 1
Details
- Title
- Selectivity of Digitalis Glycosides for Isoforms of Human Na,K-ATPase
- Creators
- Adriana Katz (null) - 972WIS_INST___112Yael Lifshitz (null)Elizabeta Bab-Dinitz (null) - 972WIS_INST___112Einat Kapri-Pardes (null)Rivka Goldshleger (null)Daniel M. Tal (null)Steven J.D Karlish (null) - 972WIS_INST___112
- Resource Type
- Journal article
- Publication Details
- Journal of Biological Chemistry, Vol.285(25), pp.19582-19592; Jun/2010
- Number of pages
- 11
- Language
- English
- DOI
- https://doi.org/10.1074/jbc.M110.119248
- Record Identifier
- 993267004203596
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