Evidence against an involvement of Na+, K+-ATPase in antiarrhythmic mechanism of phenytoin

Autor: Rhee, H. M.
Zdroj: Naunyn-Schmiedeberg's Archives of Pharmacology; June 1983, Vol. 323 Issue: 1 p78-84, 7p
Abstrakt: Phenytoin (Diphenylhydantoin, DPH) did not activate Na+, K+-ATPase activity prepared from both canine cardiac and renal tissues at any ratio of NA+ to K+ instandard assay medium and this drug failed to relieve the inhibitory effect of ouabain on Na+, K+-ATPase. With the Na+, K+-ATPase partially purified from the cardiac tissue the maximum number of ouabain binding sites was 50 pmol ouabain per mg enzyme and the dissociation constant (Kd) was 4×10-8 mol/l. Scatchard analysis of ouabain binding to Na+, K+-ATPase indicates that DPH did not significantly alter these parameters. The relase of ouabain from Na+, K+-ATPase and ouabain complex was also not significantly influenced by DPH which indicates that the antiarrhythmic action of DPH against digitalis-induced arrhythmia is not due to a simple displacement of ouabain from Na+, K+-ATPase molecules.
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