Active component of licorice as a steroid agonist; studies on the mechanism of action of glycyrrhizin

为阐明大黄素的保钠和致高血压作用，对新合成的大黄次酸（GR）的盐皮质激素（MC）活性进行了体内外研究。（1）[^3H]醛固酮的Scatchard分析表明，高亲和力位点（Ⅰ型）的Kd为6.0 × 10 ~（-1）mol/mg蛋白<-9>，Bnac为1.0 × 10 ~（-1）<-14>mol/mg蛋白;低亲和力位点（Ⅱ型）的Kd为1.6 × 10 ~（-1）mol/mg蛋白<-7>，Bmax为7.5 × 10 ~（-1）<-14>mol/mg蛋白。GR在10^4倍于未标记醛固酮的浓度下竞争肾谷溶胶中的[^3H]醛固酮结合位点。糖皮质激素受体阻断剂RU-28362取代了醛固酮结合曲线，而GR结合动力学不受化合物的影响。GR与MC受体阻断剂ZK 91587竞争[^3H]醛固酮肾细胞溶质结合。(2)GR可部分恢复去肾上腺大鼠小肠刷状缘Mg^&lt;2+&gt;-HCO^-_ -ATPase活性的下降。(3)（4）口服GR（225 mg/d，连续1周）可使大鼠尿皮质醇/皮质醇比值显著降低，提示GR对11-羟类固醇脱氢酶活性有抑制作用。

In order to elucidate the sodium-retaining and hypertensionogenic action of glycyrrhizin; an active principle of liquorice, minaralocorticoid (MC) activity of glycyrrhetinic acid (GR) which was newly synthesized, was studied in vitro and in vivo. The results were summarized as follows: (1) Scatchard analysis of [^3H] aldosterone showed that Kd of higher affinity site (type I) 6.0X10^<-9>, Bnac 1.0X10^<-14> mol/mg/protein, and Kd of lower affinity site (type II) 1.6X10^<-7>M, Bmax 7.5X10^<-14> mol/mg protein. GR competed for [^3H] aldosterone binding site in kidney sitosol at the concentration of 10^4 times as that of unlabeled aldosterone. RU-28362; glucocorticoid receptor blocker displaced aldosterone binding curve, whereas GR binding kinetic was not affected by the compound. GR competed with ZK 91587; MC receptor blocker, for [^3H]aldos teronekidney cytosol binding. (2) Decreased activity of Mg^<2+>-HCO^-_ -ATPase in brush border of the small instestine in adrenalectomized rats was partially restored by GR administration. (3) However, electrical potential differences in the adrenalectomized rats were increased in a dose-dependent manner with long-term administration of GR. (4) The oral administration of GR, in a dose of 225 mg a day for a week, caused significant decrease of the ratio of urinary cortisone to cortisol, suggesting the inhibitory effect of GR on 11-hydroxysteroid dehydrogenase activity.