The binding of 3H‐digitoxigenin by guinea‐pig atrial tissue

Abstract

1 . The uptake and release of ³H-digitoxigenin by electrically driven, guinea-pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations—1 × 10⁻⁷ and 5 × 10⁻⁷ g/ml.—caused a pronounced increase in contractile force. 2 . The uptake of ³H-digitoxigenin reached equilibrium after approximately 2 hr of incubation. At equilibrium, the tissue/medium radioactivity ratio reached a value of about 8 for both concentrations studied. After initial saturation of the atria with ³H-digitoxigenin, approximately 60% of the accumulated genin was released on wash-out in genin-free Tyrode solution for 2 hr. 3 . After presaturation of the atria with equimolar concentrations of either digitoxigenin or digitoxin (both non-radioactive) the uptake of ³H-digitoxigenin occurred more slowly. After 2 hr of incubation approximately 60–70% of the tissue bound digitoxigenin or digitoxin had exchanged against ³H-digitoxigenin from the medium. Presaturation of the atria with ouabain in equimolar concentration did not significantly affect the uptake of ³H-digitoxigenin. 4 . The release process of ³H-digitoxigenin was not affected by the same concentration of non-radioactive digitoxigenin as used for the accumulation of the genin. 5 . The kinetic properties of ³H-digitoxigenin, determined by means of isotope techniques, are very similar to those of ³H-digitoxin. The discrepancy between kinetic and pharmacological behaviour is, however, much larger for digitoxigenin than for digitoxin. Obviously, the presence or absence of the sugar moieties considerably influences the behaviour of the molecule towards the specific receptors, without particularly affecting the binding to unspecific, cellular structures.