文章基本信息

标题：Dexamethasone 21-mesylate: an affinity label of glucocorticoid receptors from rat hepatoma tissue culture cells
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作者：S S Simons ; E B Thompson
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1981
卷号：78
期号：6
页码：3541-3545
DOI：10.1073/pnas.78.6.3541
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We recently described the biological properties of an alpha-keto mesylate derivative of cortisol, cortisol-Mes. Cortisol-Mes exhibited long-term antiglucocorticoid activity, but there was no firm evidence that this activity was irreversible or receptor-mediated. Here we report that dexamethasone mesylate (Dex-Mes), which is the alpha-keto mesylate derivative of the more active glucocorticoid dexamethasone, is a candidate for a steroid-specific affinity label of glucocorticoid receptors. Dex-Mes is relatively stable, like cortisol-Mes, but possesses greater whole-cell antiglucocorticoid activity. However, Dex-Mes also possesses partial agonist activity, which is expressed at somewhat higher concentrations of Dex-Mes than the antagonist activity. Dex-Mes is more efficient than cortisol-Mes in competing for dexamethasone binding to glucocorticoid receptors. Furthermore, Dex-Mes is effective at lower concentrations than cortisol-Mes in causing long-term apparently irreversible antiglucocorticoid effects in whole and broken cells. The cell-free effect of Dex-Mes is specifically prevented by coincubation with an excess of cortisol. These facts argue that the apparently irreversible effects of Dex-Mes are steroid mediated. [3H]Dex-Mes has been used to identify a glucocorticoid-specific, covalently labeled fraction on sodium dodecyl sulfate/polyacrylamide gels with a molecular weight of approximately 85,000. Thus Dex-Mes appears to have been established as an affinity label for glucocorticoid receptors.