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Receptor occupancy with digoxin vs receptor occupancy with a putative endogenous digitalislike factor.
T A Schmidt1, H Bundgaard, K Kjeldsen
1Department of Medicine B, The Heart Centre, Rigshospitalet, Denmark.
Summary
Researchers investigated the potential existence of an endogenous digitalis-like factor. While studies showed minimal changes in ouabain binding, a significant physiological role for such a factor remains unlikely.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- The existence of an endogenous ligand for the digitalis receptor has been long speculated.
- Previous research efforts have focused on identifying this potential hormone.
Purpose of the Study:
- To investigate the possibility of an endogenous digitalis-like factor.
- To assess its potential physiological significance based on receptor binding.
Main Methods:
- Analysis of myocardial and skeletal muscle samples from non-digoxin-treated subjects.
- Measurement of 3H-ouabain binding after prolonged washing.
- Evaluation of receptor occupancy with digoxin.
Main Results:
- Prolonged washing of muscle samples showed small tendencies (2-9% and -2-7%) to increase 3H-ouabain binding.
- No significant changes in sample wet weight or water content were observed.
- Calculated digitalis receptor occupancy by digoxin suggests a putative endogenous factor would need to be present in larger quantities to be physiologically significant.
Conclusions:
- The study did not entirely rule out a quantitatively small endogenous digitalis-like factor.
- However, the observed receptor occupancy levels make a significant physiological role for such a factor improbable.