Digitalis receptor sugar binding site characteristics: A model based upon studies of Na+, K+-ATPase preparations with differing digitalis sensitivities
| Autor: | Arthur H. L. From, Khalil Ahmed, Dwight S. Fullerton |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Swine
Stereochemistry Receptors Drug Clinical Biochemistry Digitalis Kidney Models Biological Ouabain Structure-Activity Relationship chemistry.chemical_compound medicine Animals Na+/K+-ATPase Receptor Sugar Digitoxigenin Molecular Biology chemistry.chemical_classification biology Chemistry Brain Digitalis Glycosides Glycoside Cell Biology General Medicine biology.organism_classification Rats Isoenzymes Kinetics Enzyme Biochemistry Cats Rabbits Sodium-Potassium-Exchanging ATPase medicine.drug |
| Zdroj: | Molecular and Cellular Biochemistry. 94:157-165 |
| ISSN: | 1573-4919 0300-8177 |
| DOI: | 10.1007/bf00214122 |
| Popis: | The structure-activity relationships of the genin moieties of digitalis glycosides are commonly elucidated by determining the inhibitory potency of a variety of genins toward the plasma membrane Na+, K(+)-ATPase; qualitatively these relationships appear to be fairly independent of the specific Na+, K(+)-ATPase preparation utilized for the analysis. To determine whether this is the case with regard to the sugar moieties of glycosides, the inhibitory effects of 12 monoglycosides of digitoxigenin toward four Na+, K(+)-ATPase preparations of different origin were measured. It was found that while recognition of the major structural determinants of sugar activity appeared to be independent of enzyme source, recognition of the minor structural determinants of activity showed some source dependence. It was also observed that the intrinsic sensitivity to sugar potentiation may be source dependent and unrelated to intrinsic sensitivity to inhibition by digitoxigenin. These observations are compatible with a model of the Na+, K(+)-ATPase sugar binding site(s) in which intrinsic sensitivity to sugar attachment as well as recognition characteristics (for sugar structural features) both determine the extent to which a sugar moiety may contribute to the activity of monoglycosides. Further, in these studies one of the Na+, K(+)-ATPase preparations employed was obtained from rat brain, a tissue known to contain a mixture of ouabain sensitive and insensitive isoforms. We have observed that the rigorous purification techniques employed appear to have selectively removed from or denatured the less ouabain sensitive alpha 1 isoform found in this enzyme preparation. |
| Databáze: | OpenAIRE |
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