Two receptor forms for ouabain in sarcolemma-enriched preparations from canine ventricle
| Autor: | N V Wellsmith, G E Lindenmayer |
|---|---|
| Rok vydání: | 1980 |
| Předmět: |
Time Factors
Physiology Stereochemistry Receptors Drug chemistry.chemical_element Buffers Dissociation (chemistry) Ouabain Dogs Sarcolemma medicine Animals Ventricular Function Na+/K+-ATPase Receptor Cardiac glycoside chemistry.chemical_classification Binding Sites Magnesium Sodium Dodecyl Sulfate Glycoside chemistry Potassium Sodium-Potassium-Exchanging ATPase Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | Circulation Research. 47:710-720 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/01.res.47.5.710 |
| Popis: | Some evidence indicates that the inotropic effect of cardiac glycosides occurs at concentrations too low to affect Na+,K+-ATPase activity. This suggests that some receptor other than Na+,K+-ATPase mediates the inotropic effect. We studied ouabain binding to sarcolemma-enriched preparations from canine ventricle under conditions known to promote binding to Na+,K+-ATPase. Profiles for binding and dissociation were characterized by two kinetic components: (1) fast association and slow dissociation; (2) slow association and fast dissociation. Profiles in the absence of supporting ligands were consistent with a single species of receptors with slow association, fast dissociation and minimal effect on Na+,K+-ATPase activity. Binding supported by magnesium plus inorganic phosphate inhibited Na+,K+-ATPase activity by 86%. The two binding components were affected differentially by heating at 55 degrees C. It was concluded that the preparation possesses two receptors for ouabain: the Na+,K+-ATPase and a "new" receptor. The latter may be different chemically from the Na+,K+-ATPase. The more likely possibility is that the "new" receptor is the Na+,K+-ATPase in a state characterized by low catalytic activity, low affinity for ouabain, and no requirement of specific ligands for ouabain binding. Further, the data suggest an interdependence between the two forms. This leads to a mechanism which allows an inotropic effect to precede loss of Na+,K+-ATPase activity even though both result from glycoside binding to Na+,K+-ATPase. The mechanism involves an equilibrium between inactive and active forms of the Na+,K+-ATPase such that the inactive form buffers loss of the active form upon exposure to a cardiac glycoside. |
| Databáze: | OpenAIRE |
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