Mechanism of prostaglandin E2-induced arachidonic acid release in osteoblast-like cells: independence from phosphoinositide hydrolysis.
We previously reported that pertussis toxin (PTX)-sensitive GTP-binding protein is involved in the coupling of prostaglandin E2 (PGE2) receptor to phospholipase C in osteoblast-like MC3T3-E1 cells (1). In the present study, we analyzed the mechanism of PGE2-induced arachidonic acid (AA) release in MC3T3-E1 cells. PGE2 stimulated the release of AA and the formation of inositol trisphosphate (IP3) dose dependently in the range between 1 nM and 10 microM. The effect of PGE2 on AA release (ED50 was 80 nM) was more potent than that on IP3 formation (ED50 was 0.8 microM). Quinacrine, a phospholipase A2 inhibitor, suppressed the PGE2-induced AA release but had little effect on the IP3 formation. NaF, a GTP-binding protein activator, mimicked PGE2 by stimulating the AA release. The AA release stimulated by a combination of PGE2 and NaF was not additive. PTX had little effect on the PGE2-induced AA release. These results strongly suggest that the AA release and the phosphoinositide hydrolysis are separately stimulated by PGE2 in osteoblast-like cells, and the PGE2-induced AA release is mediated by PTX-insensitive GTP-binding protein.
Kozawa
O
O
Department of Biochemistry, Aichi Prefectural Colony, Japan.
Tokuda
H
H
Miwa
M
M
Takahashi
Y
Y
Ozaki
N
N
Oiso
Y
Y
D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D010006:Osteoblasts / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D011796:Quinacrine / Q000494:pharmacology; D012969:Sodium Fluoride / Q000494:pharmacology; D014316:Tritium; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D014316:Tritium; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; D012969:Sodium Fluoride; D037342:Pertussis Toxin; D011796:Quinacrine; D015232:Dinoprostone