Ipriflavone inhibits phosphoinositide hydrolysis and Ca2+ uptake in the osteoblast-like UMR-106 cells.
The mechanism of action of ipriflavone, an isoflavone derivative, was studied in the osteoblastic-like UMR-106 cell line. Ipriflavone affected both phosphoinositide hydrolysis and 45Ca2+ uptake. A repeated treatment of UMR-106 cells (once a day, for 3 days) with ipriflavone decreased, in a concentration-dependent manner, [3H]inositol monophosphate accumulation. This effect was also achieved after single addition of high concentrations of ipriflavone or 100 nM [Asu1,7]eel-calcitonin, a semi-synthetic analog of eel calcitonin. When repeatedly added to UMR-106 cells, 17 beta-estradiol produced a marked inhibition of [3H]inositol monophosphate accumulation, an effect which appeared significant only at a concentration of 1 microM and which was accompanied by a reduced incorporation of [3H]inositol into membrane phospholipids. A repeated treatment with ipriflavone reduced 45Ca2+ uptake as well. This effect was observed also after a single addition of [Asu1,7]eel-calcitonin but not following single or repeated treatment with 17 beta-estradiol. The present data indicate the osteoblast as a direct and specific target for ipriflavone and suggest that this compound may share intracellular transducing mechanisms with other antiosteoporotic hormones such as estrogen and calcitonin.
Sortino
M A
MA
Institute of Pharmacology, University of Catania, School of Medicine, Italy.
Aleppo
G
G
Scapagnini
U
U
Canonico
P L
PL
D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology; D006868:Hydrolysis; D007529:Isoflavones / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D002132:Calcium Radioisotopes; D007529:Isoflavones; D010716:Phosphatidylinositols; D004958:Estradiol; C018986:ipriflavone; D002116:Calcitonin; D002118:Calcium