Biochemical Profile of RU 486
Biochemical Profile of RU 486
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RU 486 的生化概况
DOI：
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
D. Philibert
中科院分区：
文献类型：
--
作者：
M. Moguilewsky;D. Philibert
研究了ru486与糖皮质激素受体（GR）和黄体酮受体（PR）的结合特性，以解释其抗糖皮质激素和抗黄体酮活性。在体外，（3H） ru486与（3H）地塞米松（GR）和（3H） r5020 （PR）结合相同的细胞质受体；沉降系数、结合位点数量和特异性相似。然而，（3H）RU 486对这些受体的亲和力高于强效激动剂，这可以从Scatchard图中确定的高亲和力常数和从GR和PR中缓慢的解离速率中看出。当细胞溶胶受体处于热激活状态时，激动剂能够产生更稳定的复合物。但（3H）RU 486从活化的GR中解离的速度比从未活化的GR中解离的速度快。观察到（3H）RU 486-GR复合物对dna -纤维素的亲和力比（3H）地塞米松-GR复合物低，并且RU 486在细胞核中的保留率低，这可能与RU 486缺乏糖皮质激素活性有关，从而证实了（3H）RU 486-GR复合物的激活受到阻碍。相反，子宫（3H） ru486 - pr复合物在热活化下没有加速解离速率，其对dna -纤维素的亲和力与活化后的（3H） r5020 - pr复合物相似。这导致了与ru486缺乏黄体酮活性无关的高水平核保留。与体外相互作用相反，在大鼠体内需要高剂量的RU 486才能与细胞质受体相互作用；这不能用与大鼠血浆蛋白的结合来解释。
The binding characteristics of RU 486 with the glucocorticoid receptor (GR) and the progestin receptor (PR) were studied in order to explain the potent antiglucocorticoid and antiprogestin activities of the compound. In vitro, (3H)RU 486 bound to the same cytosol receptors as (3H) dexamethasone (GR) and (3H)R 5020 (PR); the sedimentation coefficients, number of binding sites and specificity were similar. However, the affinity of (3H)RU 486 for these receptors was higher than that of the potent agonists, as indicated by the high affinity constant determined from Scatchard plots and by the slow dissociation rates from the GR and PR. With the cytosol receptor under heat activation, the agonists were able to give rise to more stable complexes, but (3H)RU 486 dissociated faster from the activated than from the non-activated GR. This impeded activation of the (3H)RU 486-GR complex was confirmed by observations of its lower affinity than that of (3H)dexamethasone-GR complex for DNA-cellulose and by a low retention in the nucleus that may be related to RU 486’s lack of glucocorticoid activity. Conversely, the uterine (3H)RU 486-PR complex did not undergo an acceleration of dissociation rate under heat activation, and its affinity for DNA-cellulose was similar to that of the activated (3H)R 5020-PR complex. This led to a high level of nuclear retention unrelated to the lack of progestin activity of RU 486. In contrast to in vitro interaction, high in vivo doses of RU 486 were needed to interact with the cytosol receptors in the rat; this cannot be explained by a binding to rat plasma protein.
糖皮质激素受体复合物的激活。
影响因子：
33.6
作者：
Schmidt,TJ;Litwack,G
通讯作者：
Litwack,G