Summary
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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Abbreviations
- Na+, K+-ATPase:
-
(Mg2+-dependent, sodium plus potassium) activated adenosinetriphosphatephohydrolase (E.C., 3.6.1.3)
- DPH:
-
5,5′-diphenylhydantoin (phenytoin)
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Rhee, H.M. Evidence against an involvement of Na+, K+-ATPase in antiarrhythmic mechanism of phenytoin. Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 78–84 (1983). https://doi.org/10.1007/BF00498832
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DOI: https://doi.org/10.1007/BF00498832