PROSTAGLANDIN-E2 IS A POTENTIAL MEDIATOR OF EXTRACELLULAR ATP ACTION IN OSTEOBLAST-LIKE CELLS

Extracellular ATP dose dependently stimulated Ca-45(2+) 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 muM 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 muM indomethacin on the DNA synthesis was reversed by adding 10 muM 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.