RU-38486 - A POTENT ANTIGLUCOCORTICOID INVITRO AND INVIVO
RU-38486 - A POTENT ANTIGLUCOCORTICOID INVITRO AND INVIVO
复制标题
DOI：
10.1016/0022-4731(85)90401-7
复制
发表时间：
1985-01-01
影响因子：
4.1
通讯作者：
PHILIBERT, D
中科院分区：
文献类型：
--
作者：
GAGNE, D;PONS, M;PHILIBERT, D
研究了RU 38486的体内外抗糖皮质激素活性。在体外研究中，RU 38486对大鼠肝癌组织培养（HTC）细胞中的胞浆糖皮质激素受体具有高亲和力（比地塞米松高3倍）。这种高亲和力是由于与受体形成的复合物的解离速率非常低。在全细胞中，它是地塞米松诱导的酪氨酸氨基转移酶（达特）活性的有效完全拮抗剂：IC 50比所用地塞米松浓度低6-7倍。其在高达10 μ M的浓度下没有任何糖皮质激素活性。在使用肾上腺切除大鼠的体内研究中，RU 38486完全抑制地塞米松诱导的肝色氨酸加氧酶（TO）活性。它也是第一个地塞米松诱导的肝达特的纯拮抗剂。然而，对于0.01 mg/kg地塞米松作用的50%抑制，需要高达5mg.kg的剂量。高达50 mg/kg的RU 38486对这两种反应均未显示任何糖皮质激素效应。
The antiglucocorticoid activity of RU 38486, was studied in vitro and in vivo. In vitro studies, RU 38486 was characterized by high affinity (3 times higher than that of dexamethasone) for the cytosolic glucocorticoid receptor in rat hepatoma tissue culture (HTC) cells. This high affinity was due to a very low dissociation rate of the complexes formed with the receptor. In whole cells it was a potent full antagonist of dexamethasone-induced tyrosine aminotransferase (TAT) activity: the IC50 was 6-7 times lower than the concentration of the dexamethasone used. It was devoid of any glucocorticoid activity up to a concentration of 10 .mu.M. In in vivo studies using adrenalectomized rats, RU 38486 totally inhibited dexamethasone-induced hepatic tryptophan oxygyenase (TO) activity. It is also the first pure antagonist of dexamethasone-induced hepatic TAT. However, doses as high as 5 mg.kg of body weight were required for a 50% inhibition of the effect of dexamethasone at 0.01 mg/kg. RU 38486 did not display any glucocorticoid effect on these two responses up to 50 mg/kg.