Mechanism of prostaglandin E 2-induced arachidonic acid release in osteoblast-like cells: Independence from phosphoinositide hydrolysis

Abstract

We previously reported that pertussis toxin (PTX)-sensitive GTP-binding protein is involved in the coupling of prostaglandin E 2 (PGE 2) receptor to phospholipase C in osteoblast-like MC3T3-E1 cells (1). In the present study, we analyzed the mechanism of PGE 2-induced arachidonic acid (AA) release in MC3T3-E1 cells. PGE 2 stimulated the release of AA and the formation of inositol trisphosphate (IP 3) dose dependently in the range between 1 nM and 10 μM. The effect of PGE 2 on AA release (ED 50 was 80 nM) was more potent than that on IP 3 formation (ED 50 was 0.8 μM). Quinacrine, a phospholipase A 2 inhibitor, suppressed the PGE 2-induced AA release but had little effect on the IP 3 formation. NaF, a GTP-binding protein activator, mimicked PGE 2 by stimulating the AA release. The AA release stimulated by a combination of PGE 2 and NaF was not additive. PTX had little effect on the PGE 2-induced AA release. These results strongly suggest that the AA release and the phosphoinositide hydrolysis are separately stimulated by PGE 2 in osteoblast-like cells, and the PGE 2-induced AA release is mediated by PTX-insensitive GTP-binding protein.