Desensitization by glycyrrhetinic acid of other stimulatory substance-induced increases in intracellular calcium in a variety of cell types.
The effects of glycyrrhizin and its aglycone, glycyrrhetinic acid, on the cytoplasmic free calcium concentration ([Ca2+]i) in mastocytoma P-815 cells, DNP-Ascaris (antigen) sensitized mast cells, hepatocytes, fibroblasts and endothelial cells were investigated. In these cell types, glycyrrhetinic acid in the concentration range of 20 to 100 microM caused an increase in [Ca2+]i and inhibited calcium increases induced by an antigen (mast cells), ATP, phenylephrine (hepatocytes) and thrombin (fibroblasts and endothelial cells). Stimulation with phenylephrine, in place of glycyrrhetinic acid, did not inhibit subsequent calcium increases induced by phenylephrine or ATP. On the other hand, glycyrrhizin at concentrations up to 100 microM neither caused an increase in [Ca2+]i nor inhibited calcium increases induced by other stimulatory substances. These results suggest that the inhibition of the calcium-mediated signal pathway may participate in the cytostatic actions of glycyrrhetinic acid.
Hayashi
Y
Y
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Hirai
S
S
Negishi
M
M
Okumura
T
T
Ichikawa
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects
D010656:Phenylephrine; D015759:Ionomycin; D000255:Adenosine Triphosphate; D006034:Glycyrrhetinic Acid; D002118:Calcium