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  • Title: Evidence against an involvement of Na+, K+-ATPase in antiarrhythmic mechanism of phenytoin.
    Author: Rhee HM.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1983 Jun; 323(1):78-84. PubMed ID: 6308480.
    Abstract:
    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+ in standard 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 X 10(-8) mol/l. Scatchard analysis of ouabain binding to Na+,K+-ATPase indicates that DPH did not significantly alter these parameters. The release 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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