title: Evidence against an involvement of Na+, K+-ATPase in antiarrhythmic mechanism of phenytoin.
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.
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents; D004285:Dogs; D007668:Kidney / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D010042:Ouabain / Q000378:metabolism; D010672:Phenytoin / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011485:Protein Binding; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D010042:Ouabain; D010672:Phenytoin; D011189:Potassium Chloride; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium