A photochemical analogue of strophanthidin, 3-azidoacetylstrophanthidin (AAS) was synthesized and tested as a cardiotropic steroid (CS) site directed photoaffinity label for Na+ + K+-ATPAse (ATP phosphohydrolase, E.C. 22.214.171.124). AAS-inhibited rat brain ATPase with an I50 of about 1 × 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.
|Number of pages||8|
|Journal||European Journal of Pharmacology|
|State||Published - Jan 1976|
Bibliographical noteFunding Information:
This work was supported by grants from the Michigan Heart Association, Grant HL 16055-01 from the National Institutes of Health, Grant BMS74-18512 from the National Science Foundation, and General Research Support Grant NIH RR 05623-04 to the College of Veterinary Medicine, Michigan State University, from the National Institutes of Health. The authors would like to thank Professor W.R. Reusch for much help and advise with the synthesis of AAS and Mrs. Annie Han for excellent technical assistance.
- Binding sites
- Cardiotonic steroids
- Na + K-ATPase
- Photoaffinity labeling
ASJC Scopus subject areas