In vitro activation of rat cardiac glucocorticoid antagonist-versus agonist-receptor complexes
| Autor: | Thomas J. Schmidt, Edward E. Diehl |
|---|---|
| Rok vydání: | 1988 |
| Předmět: |
Male
Agonist Cytoplasm Conformational change Hot Temperature Protein Conformation medicine.drug_class Triamcinolone Acetonide chemistry.chemical_compound Receptors Glucocorticoid Glucocorticoid receptor In vivo medicine Animals Estrenes Cellulose Receptor Glucocorticoids Molecular Biology Biotransformation Chemistry Myocardium Antiglucocorticoid Rats Inbred Strains DNA Cell Biology In vitro Rats Mifepristone Biochemistry Glucocorticoid medicine.drug |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 970:212-221 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/0167-4889(88)90181-4 |
| Popis: | The synthetic antiglucocorticoid RU 38486 interacts with cardiac cytoplasmic glucocorticoid receptors and competes for in vitro binding with the potent agonist triamcinolone acetonide. In addition to binding to receptors with high affinity, RU 38486 also facilitates the in vitro conformational change in the receptor which is a consequence of the physiologically relevant activation step during which the receptor is converted from a non DNA- to a DNA-binding form. This ability of RU 38486 to promote receptor activation is reflected by both the appropriate shift in the elution profile of [ 3 H]RU 38486-receptor complexes from DEAE-cellulose as well as by an increased binding of these complexes to DNA-cellulose. Although less effective than triamcinolone acetonide, RU 38486 promotes in vitro receptor activation under a variety of experimental conditions, including incubation of labeled cardiac cytosols at 25°C for 30 min or at 15°C for 30 min in the presence of 5 mM pyridoxal 5′-phosphate. Once thermally activated, the cardiac [ 3 H]triamcinolone acetonide and [ 3 H]RU 38486-receptor complexes bind to nonspecific DNA-cellulose with the same relative affinities, as evidenced by the fact that 50% of both activated complexes are eluted at approx. 215–250 mM NaCl. Thus, this pure antiglucocorticoid does promote, at least to some extent, many of the crucial in vitro events including high-affinity binding, activation, and DNA binding which have been shown to be required to elicit a physiological response in vivo. |
| Databáze: | OpenAIRE |
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