Effects of glycyrrhizin and glycyrrhetinic acid on (Na+ + K+)-ATPase of renal basolateral membranes in vitro.
Studies were made on the direct effects of glycyrrhizin and its aglycone, glycyrrhetinic acid on the activities of (Na+ + K+)-ATPase and (Ca2+ + Mg2+)-ATPase, a membrane bound Na+ and Ca2+-extrusion pump enzyme of the basolateral membranes (BLM) of canine kidney. Glycyrrhetinic acid inhibited the activity of the Na+-pump enzyme dose-dependently (IC50 = 1.5 x 10(-4) M), but had no effect on that of the Ca2+-pump enzyme of kidney BLM and homogenates. Glycyrrhizin also inhibited the Na+-pump enzyme activity but had less effect (IC50 = 2 x 10(-3) M). The effects of these compounds were due to competitive inhibition with ATP binding to the enzyme (Ki = 12 microM) and so were different from that of ouabain, which inhibits the Na+-pump by binding to its extracellular K+-binding site. The direct effect of glycyrrhetinic acid on the membrane may be important role in the multiple actions of licorice.
Itoh
K
K
Department of Medicine and Geriatrics, Osaka University Medical School, Japan.
Hara
T
T
Shiraishi
T
T
Taniguchi
K
K
Morimoto
S
S
Onishi
T
T
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002462:Cell Membrane / Q000201:enzymology; D004285:Dogs; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D000450:Aldosterone; D011374:Progesterone; D010042:Ouabain; D019695:Glycyrrhizic Acid; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D006034:Glycyrrhetinic Acid