EFFECT OF RETINOIC ACID ON PROSTAGLANDIN F-2-ALPHA-INDUCED PHOSPHOLIPASE-D ACTIVITY IN OSTEOBLAST-LIKE CELLS

We previously reported that prostaglandin F-2 alpha (PGF(2 alpha)) act ivates phosphatidylcholine-hydrolyzing phospholipase D independently f rom the activation of protein kinase C (PKC) in osteoblast-like MC3T3- E1 cells, and reported that pertussis toxin-sensitive GTP-binding prot ein (G-protein) is involved in the PGF(2 alpha)-induced phospholipase D activation. In this study, we examined the effect of retinoic acid ( RA) on the phospholipase D activity stimulated by PGF(2 alpha) in thes e cells. The pretreatment of RA markedly inhibited the formation of ch oline induced by PGF(2 alpha) (10 mu M) in a dose-dependent manner in the range between 1 nM and 0.1 mu M. This inhibitory effect of RA was dependent on the time of pretreatment up to 8 h. However, RA had littl e effect on the choline formation induced by NaF, a G-protein activato r, or 12-O-tetradecanoylphorbol-13-acetate, an activator of PKC. These results strongly suggest that RA suppresses the phospholipase D activ ated by PGF(2 alpha) in osteoblast-like cells and that the effect of R A is exerted at the point between PGF(2 alpha) receptor and G-protein.