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pubmed-article:6331370pubmed:abstractTextAffinity labelling of the digitalis receptor has indicated that it is situated on the N-terminal part of the alpha-subunit of the (Na+,K+)ATPase. Biochemical and pharmacological properties of the (Na+,K+)ATPase studied on intact chick embryonic hearts and under heart cell culture conditions have indicated the existence of two families of ouabain binding sites i.e.: a low affinity binding sites with a dissociation constant (Kd) of 2-6 microM for the ouabain-receptor complex and a high affinity binding site with a Kd of 26-48 nM. High and low affinity sites also are present at all embryonic stages studied. Inhibition of 86Rb+ uptake in cultured cardiac cells and increase in intracellular Na+ concentration, due to (Na+,K+)ATPase blockade, occur in an ouabain concentration range corresponding to the saturation of the low affinity ouabain site. Ouabain stimulated 45Ca2+ uptake increases in parallel with the increase in the intracellular Na+ concentration. It is suppressed in Na+ free medium or when Na+ is replaced by Li+ suggesting that the increase is due to the indirect activation of the Na+/Ca2+ exchange system in the plasma membrane. Dose-response curves for the inotropic effects of ouabain on papillary muscle and on ventricular cells in culture indicate the development of the cardiotonic properties is parallel to the saturation of the low affinity binding site for ouabain. Therefore, inhibition of the cardiac (Na+,K+)ATPase corresponding to low affinity ouabain binding sites seems to be responsible for both the cardiotonic and cardiotoxic effects of the drug.lld:pubmed
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pubmed-article:6331370pubmed:dateRevised2007-11-15lld:pubmed
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pubmed-article:6331370pubmed:articleTitleDigitalis receptors affinity labelling and relation with positive inotropic and cardiotoxic effects.lld:pubmed
pubmed-article:6331370pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:6331370pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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