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

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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.