Abstract
1. The ability of isolated perfused guinea-pig (digitalis-sensitive species) and rat (digitalis-resistant species) hearts to accumulate radio-labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium.
2. It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin.
3. The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non-polar glycosides.
4. The low accumulation of all digitaloids by the rat heart in comparison to the guinea-pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea-pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non-polar glycosides.
5. It was concluded that non-polar glycosides such as digitoxin and proscillaridin demonstrate the same ion-dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non-polar glycosides possess high capacity for ion-independent binding presumably due to lipophilic interactions with membranes.
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Selected References
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- Albers R. W., Koval G. J., Siegel Studies on the interaction of ouabain and other cardio-active steroids with sodium-potassium-activated adenosine triphosphatase. Mol Pharmacol. 1968 Jul;4(4):324–336. [PubMed] [Google Scholar]
- Allen J. C., Schwartz A. A possible biochemical explanation for the insensitivity of the rat to cardiac glycosides. J Pharmacol Exp Ther. 1969 Jul;168(1):42–46. [PubMed] [Google Scholar]
- Baker P. F., Willis J. S. Potassium ions and the binding of cardiac glycosides to mammalian cells. Nature. 1970 May 9;226(5245):521–523. doi: 10.1038/226521a0. [DOI] [PubMed] [Google Scholar]
- Caprio A., Farah A. The effect of the ionic milieu on the response of rabbit cardiac muscle to ouabain. J Pharmacol Exp Ther. 1967 Mar;155(3):403–414. [PubMed] [Google Scholar]
- Dutta S., Goswami S., Datta D. K., Lindower J. O., Marks B. H. The uptake and binding of six radiolabeled cardiac glycosides by guinea-pig hearts and by isolated sarcoplasmic reticulum. J Pharmacol Exp Ther. 1968 Nov;164(1):10–21. [PubMed] [Google Scholar]
- Dutta S., Marks B. H. Factors that regulate ouabain-H3 accumulation by the isolated guinea-pig heart. J Pharmacol Exp Ther. 1969 Dec;170(2):318–325. [PubMed] [Google Scholar]
- Ito M., Hollander P. B., Marks B. H., Dutta S. The effects of six cardiac glycosides on the transmembrane potential and contractile characteristics of the right ventricle of guinea pigs. J Pharmacol Exp Ther. 1970 Mar;172(1):188–195. [PubMed] [Google Scholar]
- Kuschinsky K., Lüllmann H., van Zwieten P. A. A comparison of the accumulation and release of 3H-ouabain and 3H-digitoxin by guinea-pig heart muscle. Br J Pharmacol Chemother. 1968 Mar;32(3):598–608. doi: 10.1111/j.1476-5381.1968.tb00460.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Talbot M. S. Sodium dependence of the rate of onset of the ouabain-induced positive inotropic effect on cardiac muscle. Nature. 1968 Sep 7;219(5158):1053–1054. doi: 10.1038/2191053b0. [DOI] [PubMed] [Google Scholar]
- Toda N., West T. C. Modification by sodium and calcium of the cardiotoxicity induced by ouabain. J Pharmacol Exp Ther. 1966 Nov;154(2):239–249. [PubMed] [Google Scholar]