Comparative ability of digoxin and an aminosugar cardiac glycoside to bind to and inhibit Na+,K+-adenosine triphosphatase. Effect of potassium

Emel Songu-Mize, Janet L. Gunter, Robert William Caldwell

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8 Scopus citations

Abstract

We compared the abilities of digoxin and aminogalactose digitoxigenin (ASI-222) to bind to, or inhibit, purified dog heart Na+,K+-ATPase in the presence of 1, 10, or 80 mM potassium chloride. Changing the potassium concentration from 1 to 10 mM increased the dose producing 50% inhibition of enzyme activity (IC50) by 9- and 2.5-fold for digoxin and ASI-222 respectively. Raising the potassium concentration to 80 mM increased the IC50 for digoxin 3-fold but did not alter significantly the IC50 for ASI-222. Equilibrium binding studies showed that this enzyme exhibited a single class of specific binding sites for both digoxin and ASI-222. Raising the potassium concentration did not affect the maximum number of binding sites (Bmax) but increased the apparent dissociation constant (KD) for digoxin. Potassium differentially affected the affinity and number of binding sites for ASI-222; raising the potassium concentration from 1 to 10 mM did not affect the Bmax or the KD, but raising it to 80 mM increased both. The effect of i.v. infusion of potassium chloride upon cardiac arrhythmias produced by i.v. infusion of digoxin or ASI-222 in anesthetized dogs was also determined. Infusion of potassium chloride reversed the cardiac arrhythmias due to digoxin to normal rhythm, but not those due to ASI-222. In conclusion, the interaction of digoxin and the polar digitals agent, ASI-222, with dog heart Na+,K+-ATPase was differentially affected by potassium. These agents also produced cardiac arrhythmias, which were differentially affected by potassium.

Original languageEnglish (US)
Pages (from-to)3689-3695
Number of pages7
JournalBiochemical Pharmacology
Volume38
Issue number21
DOIs
Publication statusPublished - Nov 1 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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