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Journal of Pharmacology And Experimental Therapeutics, Vol. 168, Issue 1, 31-41, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics


POSSIBLE INVOLVEMENT OF CARDIAC Na+ , K+-ADENOSINE TRIPHOSPHATASE IN THE MECHANISM OF ACTION OF CARDIAC GLYCOSIDES

ARNOLD SCHWARTZ 1, JULIUS C. ALLEN 1, and SHOICHI HARIGAYA 1

1 Department of Pharmacology, Division of Myocardial Biology, Baylor College of Medicine, Houston, Texas

The effects of ouabain and digoxin on a cardiac Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) from dog and beef were monitored with a continuous recording spectrophotometer. A time and temperature dependence of glycoside-induced inhibition was found. Increasing the time of enzyme exposure to the drug and increasing the temperature of incubation resulted in a significant enhancement of cardiac glycoside action. Half-maximal inhibitory concentration at 45°C and after 30-minute exposure was 0.025 µM for beef heart. The binding of H3-ouabain to the Na+ , K+-ATPase appeared to be related to the inhibitory effect of ouabain on Na+, K+-ATPase. An active cardiac relaxing system did not bind H3-digoxin or H3-ouabain, nor was Ca++ binding or uptake affected by a wide range of glycoside concentrations. Cardiac mitochondria were not affected by ouabain or digoxin. It is concluded that the Na+, K+-ATPase may be involved in the action of cardiac glycosides.

Submitted on August 22, 1968
Accepted on April 3, 1969




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Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics.