Suzuki A, Kotoyori J, Oiso Y, Kozawa O
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Cell Adhes Commun. 1993 Sep;1(2):113-8. doi: 10.3109/15419069309095687.
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.
即使在存在硝苯地平（一种抑制电压依赖性钙通道的钙拮抗剂）的情况下，细胞外ATP仍能剂量依赖性地刺激成骨样MC3T3-E1细胞中的45Ca2+内流。ATP刺激花生四烯酸释放和前列腺素E2（PGE2）的合成。然而，用EGTA螯合细胞外Ca2+可显著降低ATP诱导的花生四烯酸释放。另一方面，ATP在1 microM至1 mM的范围内以剂量依赖性方式诱导这些细胞的DNA合成。用环氧化酶抑制剂吲哚美辛预处理可抑制这些细胞中ATP诱导的PGE2合成和DNA合成。添加10 microM PGE2可逆转50 microM吲哚美辛对DNA合成的抑制作用。这些结果强烈表明，细胞外ATP刺激Ca2+内流，导致成骨样细胞中花生四烯酸释放，并且细胞外ATP诱导的增殖作用至少部分由ATP刺激的PGE2合成介导。
