Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors

Abstract

Whether the mineralocorticoid effect of glycyrrhetinic acid is mediated by the adrenal glands or is due to a direct action on the renal tubule remains controversial. The affinity of glycyrrhetinic acid for mineralocorticoid receptors has been studied by several types of competition experiments. When rat kidney slices were incubated with 2 × 10-9 M [3H]aldosterone, glycyrrhetinic acid (2 × 10-5 M) was able to compete with aldosterone for the cytosolic receptor and to decrease the formation of a chromatin-[3H] aldosterone- receptor complex. In cytosol, in vitro, 6 × 10-4 M glycyrrhetinic acid was able to inhibit aldosterone binding by 70%, whereas the same dose produced only a 20% inhibition of dexamethasone binding. The apparent KDIss of glycyrrhetinic acid for the mineralocorticoid receptor was 2 × 10-6 M. That glycyrrhetinic acid appeared to compete mainly with mineralocorticoid receptors was confirmed by sedimentation in sucrose gradients: [3H]Aldosterone specifically bound to an 8 S peak was displaced by 5 × 10-5 M glycyrrhetinic acid, whereas the [3H]dexamethasone peak was not affected by this compound. Glycyrrhizic acid showed no significant affinity for mineralocorticoid or glucocorticoid kidney receptor sites. Glycyrrhetinic acid and glycyrrhizic acid had no affinity for rat cortisol binding globulin. Glycyrrhetinic acid has a low but definite affinity for mineralocorticoid receptors and thus appears to have a direct mineralocorticoid action. The low affinity of this compound for mineralocorticoid receptors is in good agreement with the very high doses required to exhibit its biological activity. © 1975 by The Endocrine Society.