Effect of glucocorticoid on prostaglandin F2 alpha-induced prostaglandin E2 synthesis in osteoblast-like cells: inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2.
It is well known that osteoporosis is a common complication of patients with glucocorticoid excess. We showed previously that prostaglandin (PG) F2 alpha stimulates the synthesis of PGE2, a potent bone resorbing agent, and that the activation of protein kinase C amplifies the PGF2 alpha-induced PGE2 synthesis through the potentiation of phospholipase A2 activity in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of dexamethasone on PGE2 synthesis induced by PGF2 alpha in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited the PGE2 synthesis in a dose-dependent manner in the range between 0.1 and 10 nmol/l in these cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited PGE2 synthesis induced by melittin, known as a phospholipase A2 activator. Furthermore, dexamethasone significantly inhibited the enhancement of PGF2 alpha- or melittin-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, known as a protein kinase C activator. In addition, dexamethasone significantly inhibited PGF2 alpha-induced formation of inositol phosphates in a dose-dependent manner between 0.1 and 10 nmol/l in MC3T3-E1 cells. These results strongly suggest that glucocorticoid inhibits PGF2 alpha-induced PGE2 synthesis through the inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A2 in osteoblast-like cells.
Department of Biochemistry, Aichi Prefectural Colony, Japan.
O
O
Kozawa
H
H
Tokuda
A
A
Suzuki
J
J
Kotoyori
Y
Y
Ito
Y
Y
Oiso
D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D006868:Hydrolysis; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D010716:Phosphatidylinositols; D008555:Melitten; D003907:Dexamethasone; D015237:Dinoprost; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate