title: Dehydro-digitoxosides of digitoxigenin and digoxigenin: binding to beef heart (Na+ + K+)-ATPase in relation to unchanged digitoxosides.
abstract: Dehydro-digitoxosides are metabolites of digitalis glycosides. In order to study their possible biological activity their affinity to (Na+ + K+)-activated ATPase was determined and compared with unchanged glycosides. Based on the dissociation constants of glycoside-enzyme-complexes, the affinity of the dehydro-digitoxosides ranged in the same order of magnitude as that of the native glycosides. Comparing mono-, bis-, and tris-digitoxosides of digitoxigenin (dt-1, dt-2, dt-3) and of digoxin (dg-1, dg-2, dg-3) with the corresponding dehydrodigitoxosides (3'-dehydro-dt-1, 9'-dehydro-dt-2, 15'-dehydro-dt3, 3'-dehydro-dg-1 and 9'-dehydro-dg-2, respectively) the dehydro-digitoxosides had lower affinities to the enzyme. The highest dissociation constants (KD) were found for 3'-dehydro-dt-1 and 3'-dehydro-dg-1. The half maximal inhibition of (Na+ + K+)-ATPase activity (I50) coresponded to affinity measurements in all but two cases: dehydro-dt-3 and dehydro-dt-2 showed very low I50 values.
mesh_terms: D000818:Animals; D001711:Biotransformation; D002417:Cattle; D004073:Digitoxigenin / Q000031:analogs & derivatives* / Q000378:metabolism; D004076:Digoxigenin / Q000031:analogs & derivatives* / Q000378:metabolism; D004077:Digoxin / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004073:Digitoxigenin; D010042:Ouabain; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D004076:Digoxigenin