Biomaterial Database

Binding of glycyrrhetinic acid to kidney mineralocorticoid and glucocorticoid receptors. 1975

A Ulmann, and J Menard, and P Corvol

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 times 10- minus 9 M [3H]aldosterone, glycyrrhetinic acid (2 times 10- minus 5 M) was able to compete with aldosterone for the cytosolic receptor and to decrease the formation of a chromatin-[3Hi1 aldosterone-receptor complex. In cytosol, in vitro, 6 times 10- minus 4 M glycyrrhetinic acid was able to inhibit aldosterone binding by 70 percent, whereas the same dose produced only a 20 percent inhibition of dexamethasone binding. The apparent KDiss of glycyrrhetinic acid for the mineralocorticoid receptor was 2 times 10- minus 6 M. That glycyrrhetinic acid appeared to compete mainly with mineralocorticoid receptors was confirmed by sedimentation in the sucrose gradients: [3H]Aldosterone specifically bound to an 8 S peak was displaced by 5 times 10- minus 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.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D008901	Mineralocorticoids	A group of CORTICOSTEROIDS primarily associated with water and electrolyte balance. This is accomplished through the effect on ION TRANSPORT in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by PLASMA VOLUME, serum potassium, and ANGIOTENSIN II.	Mineralocorticoid,Mineralocorticoid Effect,Mineralocorticoid Effects,Effect, Mineralocorticoid,Effects, Mineralocorticoid
D010946	Plants, Medicinal	Plants whose roots, leaves, seeds, bark, or other constituent parts possess therapeutic, tonic, purgative, curative or other pharmacologic attributes, when administered to man or animals.	Herbs, Medicinal,Medicinal Herbs,Healing Plants,Medicinal Plants,Pharmaceutical Plants,Healing Plant,Herb, Medicinal,Medicinal Herb,Medicinal Plant,Pharmaceutical Plant,Plant, Healing,Plant, Medicinal,Plant, Pharmaceutical,Plants, Healing,Plants, Pharmaceutical
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D003345	Corticosterone	An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D003907	Dexamethasone	An anti-inflammatory 9-fluoro-glucocorticoid.	Hexadecadrol,Decaject,Decaject-L.A.,Decameth,Decaspray,Dexasone,Dexpak,Hexadrol,Maxidex,Methylfluorprednisolone,Millicorten,Oradexon,Decaject L.A.
D005938	Glucocorticoids	A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.	Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid