Effect of retinoic acid on prostaglandin F2 alpha-induced prostaglandin E2 synthesis in osteoblast-like cells.
We previously reported that prostaglandin F2 alpha (PGF2 alpha) stimulates phosphoinositide hydrolysis via pertussis toxin-sensitive GTP-binding protein in osteoblast-like MC3T3-E1 cells (Miwa, Tokuda, Tsushita, Kotoyori, Takahashi, Ozaki, Kozawa and Oiso 1990) and that PGF2 alpha stimulates arachidonic acid release and prostaglandin E2 (PGE2) synthesis, and the activation of protein kinase C (PKC) amplifies the effect of PGF2 alpha in MC3T3-E1 cells (Tokuda, Oiso and Kozawa 1992). In the present study, we investigated the effect of retinoic acid (RA), a vitamin A (retinol) metabolite, on PGF2 alpha-induced PGE2 synthesis in MC3T3-E1 cells. The pretreatment with RA, which by itself had little effect on synthesis, significantly inhibited PGE2 synthesis induced by PGF2 alpha in a dose-dependent manner in the range between 1 nM and 0.1 microM. This effect of RA was dependent on the time of pretreatment up to 8 h. In addition, RA inhibited the amplification of PGF2 alpha-induced PGE2 synthesis by 12-O-tetradecanoylphorbol-13-acetate, known to be a PKC activator. However, RA had little effect on PGE2 synthesis induced by melittin, known as a phospholipase A2 activator. Moreover, pertussis toxin had little effect on arachidonic acid release induced by PGF2 alpha. These results strongly suggest that RA inhibits PGE2 synthesis induced by PGF2 alpha in osteoblast-like cells and the inhibitory effect is exerted at the point prior to the activation of phospholipase A2.
Kozawa
O
O
Department of Biochemistry, Institute for Developmental Research, Aichi Prefectural Colony, Japan.
Suzuki
A
A
Tokuda
H
H
Kotoyori
J
J
Ito
Y
Y
Oiso
Y
Y
D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D008555:Melitten / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D037342:Pertussis Toxin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D008555:Melitten; D014212:Tretinoin; D015237:Dinoprost; D037342:Pertussis Toxin; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate