title: Prostaglandin E2 is a potential mediator of extracellular ATP action in osteoblast-like cells.
abstract: Extracellular ATP dose dependently stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel, in osteoblast-like MC3T3-E1 cells. ATP stimulated arachidonic acid release and the synthesis of prostaglandin E2 (PGE2). However, the ATP-induced arachidonic acid release was significantly reduced by chelating extracellular Ca2+ with EGTA. On the other hand, ATP induced DNA synthesis of these cells in a dose-dependent manner in the range between 1 microM and 1 mM. The pretreatment with indomethacin, a cyclooxygenase inhibitor, suppressed both ATP-induced PGE2 synthesis and DNA synthesis in these cells. The inhibitory effect by 50 microM indomethacin on the DNA synthesis was reversed by adding 10 microM PGE2. These results strongly suggest that extracellular ATP stimulates Ca2+ influx resulting in the release of arachidonic acid in osteoblast-like cells and that extracellular ATP-induced proliferative effect is mediated, at least in part, by ATP-stimulated PGE2 synthesis.
authors.affiliation: First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Kotoyori
authors.forename: Y
authors.initials: Y
authors.lastname: Oiso
authors.forename: O
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis* / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016718:Arachidonic Acid; D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D004247:DNA; D015232:Dinoprostone; D002118:Calcium; D007213:Indomethacin