EFFECT OF RETINOIC ACID ON PROSTAGLANDIN F-2-ALPHA-INDUCED PROSTAGLANDIN E(2) SYNTHESIS IN OSTEOBLAST-LIKE CELLS

We previously reported that prostaglandin F-2 alpha (PGF(2 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 PGF(2 alpha) stimulates arachidonic acid release and prostaglandin E(2) (PGE(2)) synthesis, and the activation of protein kinase C (PKC) amplifies the effect of PGF(2 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 PGF(2 alpha)-induced PGE(2) synthesis in MC3T3-E1 cells. The pretreatment with RA, which by itself had little effect on synthesis, significantly inhibited PGE(2) synthesis induced by PGF(2 alpha) in a dose-dependent manner in the range between 1 nM and 0.1 mu M. This effect of RA was dependent on the time of pretreatment up to 8 h. In addition, RA inhibited the amplification of PGF(2 alpha)-induced PGE(2) synthesis by 12-O-tetradecanoylphorbol-13-acetate, known to be a PKC activator. However, RA had little effect on PGE(2) synthesis induced by melittin, known as a phospholipase A(2) activator. Moreover, pertussis toxin had little effect on arachidonic acid release induced by PGF(2 alpha). These results strongly suggest that RA inhibits PGE(2) synthesis induced by PGF(2 alpha) in osteoblast-like cells and the inhibitory effect is exerted at the point prior to the activation of phospholipase A(2).