Cardiotonic site directed irreversible inhibition of Na+ + K+-ATPase by 3-azidoacetylstrophanthidin, a photochemical analogue of strophanthidin.
A photochemical analogue of strophanthidin, 3-azidoacetylstrophanthidin (AAS) was synthesized and tested as a cardiotonic steroid (CS) site directed photoaffinity label for Na+ + K+-ATPase (ATP phosphohydrolase, E.C. 3.6.1.3). AAS-inhibited rat brain ATPase with an I50 of about 1 x 10(-6) M readily displaced 3H-ouabain from its specific binding sites on this enzyme and produced a positive inotropic effect in guinea pig atrial strips. In the absence of UV light its interaction with the CS binding sites of Na+ + K+-ATPase appeared reversible. In the presence of UV light and acetylphosphate, AAS produced about 15% irreversible inhibition of Na+ + K+-ATPase, compared with about 5% irreversible inhibition in the absence of either UV light or acetyl phosphate. Since acetylphosphate supports specific glucoside binding at the CS binding sites of Na+ + K+-ATPase these data are consistent with the concept that AAS is a cardiotonic steroid site directed photoactivatable inhibitor of Na+ + K+-ATPase.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010777:Photochemistry; D011188:Potassium; D051381:Rats; D012964:Sodium; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology*; D013328:Strophanthins / Q000494:pharmacology*; D013997:Time Factors
D013328:Strophanthins; D013327:Strophanthidin; D012964:Sodium; D000251:Adenosine Triphosphatases; D011188:Potassium