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

  • H. M. Rhee
Article
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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.

Key words

Antiarrhythmic agent Diphenylhydantoin Na+, K+-ATPase activity Ouabain binding 

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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Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • H. M. Rhee
    • 1
  1. 1.Department of PharmacologyOral Roberts University School of MedicineTulsaUSA

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