Proliferative effect of PGD2 on osteoblast-like cells; independent activation of pertussis toxin-sensitive GTP-binding protein from PGE2 or PGF2 alpha.
PGD2 stimulated DNA synthesis and decreased alkaline phosphatase activity dose-dependently between 10 nM and 10 microM in osteoblast-like MC3T3-E1 cells. PGD2 had little effect on cAMP production, but caused very rapid enhancement of phosphoinositide (PI) hydrolysis dose-dependently between 10 nM and 10 microM. The formation of inositol trisphosphate (IP3) induced by PGD2 reached the peak within 1 min and decreased thereafter, which is more rapid than that induced by PGE2 or PGF2 alpha and both PGE2 and PGF2 alpha affected PGD2-induced IP3 formation additively. Pertussis toxin (PTX) inhibited both PGD2-induced formation of inositol phosphates and DNA synthesis. The degree of these PTX (1 micrograms/ml)-induced inhibitions was similar. In addition, neomycin, a phospholipase C inhibitor, inhibited PGD2-induced DNA synthesis as well as the formation of IP3, and the patterns of both inhibitions were similar. In the cell membranes, PTX-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGD2. Time course of the attenuation of PTX-catalyzed ADP-ribosylation by PGD2 was apparently different from that by PGE2 or PGF2 alpha. These results indicate that PGD2 activates PTX-sensitive GTP-binding protein independently from PGE2 or PGF2 alpha and stimulates PI hydrolysis resulting in proliferation of osteoblast-like cells.
Tsushita
K
K
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kozawa
O
O
Tokuda
H
H
Oiso
Y
Y
Saito
H
H
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D009355:Neomycin / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D015230:Prostaglandin D2 / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D004247:DNA; D015237:Dinoprost; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000469:Alkaline Phosphatase; D019204:GTP-Binding Proteins; D009355:Neomycin; D015232:Dinoprostone; D015230:Prostaglandin D2