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Journal of Pharmacology And Experimental Therapeutics, Vol. 168, Issue 1, 42-46, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics


A POSSIBLE BIOCHEMICAL EXPLANATION FOR THE INSENSITIVITY OF THE RAT TO CARDIAC GLYCOSIDFJS

JULIUS C. ALLEN 1 and ARNOLD SCHWARTZ 1

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

The inhibitory effect of ouabain on Na+, K+-adenosine triphosphatase (Na+, K+-ATPase) from rat kidney and heart was found to be both temperature-and time-insensitive. Stoichiometric studies of H3-glycoside binding to rat enzyme preparations revealed a 2:1 or 3:1 relationship, whereas beef and dog preparations exhibited a 1:1 relationship (amount of glycoside bound per unit of enzyme activity). The beef and dog Na+, K+-ATPases were significantly more sensitive than rat Na+, K+-ATPases to both ouabain-induced inhibition and H3-glycoside binding. The complex formed between cardiac glycoside and the Na+ , K+-ATPase of digitalis-sensitive species appears to be much more stable than the complex formed between the Na+, K+-ATPase of rat and the glycoside. The data suggest that specific characteristics of the rat Na+, K+-ATPase which differ from those of sensitive species may explain the insensitivity of the rat to digitalis drugs.

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.