Tokuda H, Kotoyori J, Oiso Y, Kozawa O
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Endocr J. 1994 Apr;41(2):189-95. doi: 10.1507/endocrj.41.189.
Bradykinin is recognized to be involved in the process of bone resorption in chronic inflammatory diseases. We previously reported that prostaglandin E2 (PGE2), known as a potent bone resorbing agent, induces phosphoinositide hydrolysis, cAMP production and Ca2+ influx in osteoblast-like MC3T3-E1 cells, and these dose-dependencies are different to one another. To clarify the signaling mechanism of bradykinin, we compared the intracellular signaling system of bradykinin with that of PGE2 in these cells. Bradykinin stimulated Ca2+ influx dose-dependently in the range between 0.1 nM and 0.1 microM even in the presence of nifedipine, a Ca2+ antagonist that inhibits the voltage-dependent L-type Ca2+ channel. The maximum effect of bradykinin (0.1 microM) on Ca2+ influx was almost as great as that of PGE2 (0.5 microM). Bradykinin had little effect on cAMP accumulation, while PGE2 significantly stimulated it. Bradykinin stimulated the formation of inositol phosphates much less strongly than PGE2. Bradykinin stimulated inositol 1, 4, 5-trisphosphate [Ins(1, 4, 5)P3] formation dose-dependently between 0.1 nM and 0.1 microM, and the dose-dependent curves of bradykinin-induced Ca2+ influx and Ins(1, 4, 5)P3 were similar. However, the maximum effect of PGE2 (10 microM) on Ins (1, 4, 5) P3 formation was about 2-fold higher than that of bradykinin (0.1 microM). These results suggest that bradykinin induces Ca2+ influx independent of the voltage-dependent L-type Ca2+ channel and phosphoinositide hydrolysis in a similar dose-dependent manner in osteoblast-like cells.
缓激肽被认为参与慢性炎症性疾病中的骨吸收过程。我们之前报道过，前列腺素E2（PGE2）作为一种强效的骨吸收剂，可诱导成骨样MC3T3-E1细胞中的磷酸肌醇水解、cAMP生成和Ca2+内流，且这些剂量依赖性彼此不同。为了阐明缓激肽的信号传导机制，我们在这些细胞中比较了缓激肽与PGE2的细胞内信号系统。即使存在抑制电压依赖性L型Ca2+通道的Ca2+拮抗剂硝苯地平，缓激肽在0.1 nM至0.1 μM范围内仍能剂量依赖性地刺激Ca2+内流。缓激肽（0.1 μM）对Ca2+内流的最大作用几乎与PGE2（0.5 μM）相同。缓激肽对cAMP积累影响很小，而PGE2能显著刺激其积累。缓激肽刺激肌醇磷酸形成的强度远低于PGE2。缓激肽在0.1 nM至0.1 μM范围内剂量依赖性地刺激肌醇1,4,5-三磷酸[Ins(1,4,5)P3]形成，且缓激肽诱导的Ca2+内流和Ins(1,4,5)P3的剂量依赖性曲线相似。然而，PGE2（10 μM）对Ins(1,4,5)P3形成的最大作用比缓激肽（0.1 μM）高约2倍。这些结果表明，缓激肽在成骨样细胞中以类似的剂量依赖性方式诱导Ca2+内流，且不依赖于电压依赖性L型Ca2+通道和磷酸肌醇水解。
