STUDIES ON THE MECHANISM OF THE DESOXYCORTICOSTERONE (DOC)-LIKE ACTIONS OF GLYCYRRHETINIC ACID IN THE RAT

Glycyrrhetinic acid has been shown to have DOC-like actions. Thus, it produces retention of sodium and water, and increases potassium excretion in animals and man. However, its mechanism of action is not well understood. It has been suggested that the DOC-like action of glycyrrhetinic acid is due to inhibition of the metabolic inactivation of the adrenal cortical hormones by the drug. In opposition to this is the opinion that as the structure of glycyrrhetinic acid resembles that of DOC in certain respects, the drug by itself can produce DOC-like action. In view of the above contradiction, an attempt was made to explore into the mechanism by which glycyrrhetinic acid exerts its actions on electrolyte and water metabolism. Female rats weighing 140-180 grams were injected intramuscularly with 25 mg of glycyrrhetinic acid per rat, and were then given 5 ml of 0.45% NaCl solution per 100 grams body weight. The urine volume and sodium excreted in 6 hours decreased markedly, and the ratio of urine Na/K was also lowered despite of the fact that the po- tassium excretion was unchanged. Here, the action of the drug was slightly more potent than that of 1 mg of DOCA. Spironolactone, an aldosterone antagonist, at a dose of 5 mg per rat significantly antagonized the sodium- and water- retaining actions of both glycyrrhetinic acid and DOCA. Nevertheless, the action of glycyrrhetinic acid was blocked to a lesser extent than that of DOCA. △⁶-6-Methyl-cortisone acetate, a steroid with antiphlogistic and diuretic actions, markedly antagonized the actions of DOCA, but not those of glycyrrhetinic acid. The above results are in favour of the hypothesis that the DOC-like action of glycyrrhetinic acid is the result of a direct action on the function of the kidney.