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Research ArticleArticle

CORRELATION OF THE SUBCELLULAR DISTRIBUTION OF DIGOXIN WITH THE POSITIVE INOTROPIC EFFECT

NAK DOO KIM, LESLIE E. BAILEY and PETER E. DRESEL
Journal of Pharmacology and Experimental Therapeutics May 1972, 181 (2) 377-385;
NAK DOO KIM
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LESLIE E. BAILEY
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PETER E. DRESEL
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Abstract

We have investigated the effect of chlorpromazine and aldosterone on the positive inotropic effect and the subcellular distribution of 3H-digoxin in isolated, electrically driven guinea-pig hearts. Both drugs decreased the positive inotropic effect of 3H-digoxin and the uptake of the drug by the microsomal fraction, whereas the total tissue uptake and the tissue/medium ratio of the radioactivity did not differ significantly from control. Because all measurements were made in the same experiments, we were able to show a significant correlation between the positive inotropic effect and the content of 3H-digoxin in a crude microsomal fraction, but not in the mitochondrial or nuclear fractions. A significant fraction of the bound drug was released into the supernatant when the microsomal pellet was shaken in Krebs' solution and recentrifuged. There was a greater correlation of the inotropic effect with the loosely bound drug than with the total microsomal binding; there was no correlation between contractility and the drug remaining in the microsomal pellet. Gel filtration of the supernatant showed that the drug was not bound to a macromolecule. We suggest that the digoxin taken up by the cell and bound loosely to a constituent of the microsomal fraction is responsible for the positive inotropic effect.

Footnotes

    • Received March 16, 1971.
    • Accepted January 9, 1972.
  • © 1972 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 181, Issue 2
1 May 1972
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Research ArticleArticle

CORRELATION OF THE SUBCELLULAR DISTRIBUTION OF DIGOXIN WITH THE POSITIVE INOTROPIC EFFECT

NAK DOO KIM, LESLIE E. BAILEY and PETER E. DRESEL
Journal of Pharmacology and Experimental Therapeutics May 1, 1972, 181 (2) 377-385;

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Research ArticleArticle

CORRELATION OF THE SUBCELLULAR DISTRIBUTION OF DIGOXIN WITH THE POSITIVE INOTROPIC EFFECT

NAK DOO KIM, LESLIE E. BAILEY and PETER E. DRESEL
Journal of Pharmacology and Experimental Therapeutics May 1, 1972, 181 (2) 377-385;
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