TY - JOUR T1 - POSSIBLE INVOLVEMENT OF CARDIAC Na<sup>+</sup> , K<sup>+</sup>-ADENOSINE TRIPHOSPHATASE IN THE MECHANISM OF ACTION OF CARDIAC GLYCOSIDES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 31 LP - 41 VL - 168 IS - 1 AU - ARNOLD SCHWARTZ AU - JULIUS C. ALLEN AU - SHOICHI HARIGAYA Y1 - 1969/07/01 UR - http://jpet.aspetjournals.org/content/168/1/31.abstract N2 - 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. © 1969, by The Williams &amp; Wilkins Company ER -