Suzuki N, Matsunaga T, Kanaho Y, Nozawa Y
Department of Orthopaedic Surgery, Gifu University, School of Medicine, Japan.
Nihon Seikeigeka Gakkai Zasshi. 1993 Oct;67(10):935-43.
In the present study, we investigated the mechanism by which bradykinin (BK) enhances [3H]arachidonic acid release in murine osteoblast-like MC3T3-E1 cells prelabeled with [3H]arachidonic acid. BK enhanced [3H]arachidonic acid release in a time- and concentration-dependent manner, when cells were stimulated in the presence, but not in the absence, of extracellular Ca2+. It appears that the BK-induced [3H]arachidonic acid release was attributed to the activation of phospholipase A2, since a phospholipase A2 inhibitor, mepacrine, significantly inhibited the BK enhancement of [3H]arachidonic acid release whereas a diacylglycerol lipase inhibitor, RHC80267, failed to do so. Furthermore, it was found that a protein kinase C inhibitor, staurosporine, and down-regulation of protein kinase C by prolonged exposure of cells to phorbol 12-myristate 13-acetate inhibited the BK-induced [3H]arachidonic acid release. These results provide evidence that BK stimulation of MC3T3-E1 cells activates phospholipase A2 to liberate arachidonic acid by the mechanism which involves both Ca2+ and protein kinase C.
在本研究中，我们探究了缓激肽（BK）增强预先用[3H]花生四烯酸标记的小鼠成骨样MC3T3-E1细胞中[3H]花生四烯酸释放的机制。当细胞在细胞外Ca2+存在而非不存在的情况下受到刺激时，BK以时间和浓度依赖性方式增强了[3H]花生四烯酸的释放。BK诱导的[3H]花生四烯酸释放似乎归因于磷脂酶A2的激活，因为磷脂酶A2抑制剂米帕林显著抑制了BK对[3H]花生四烯酸释放的增强作用，而二酰基甘油脂肪酶抑制剂RHC80267则未能做到这一点。此外，还发现蛋白激酶C抑制剂星形孢菌素以及通过使细胞长期暴露于佛波醇12-肉豆蔻酸酯13-乙酸酯来下调蛋白激酶C，均抑制了BK诱导的[3H]花生四烯酸释放。这些结果提供了证据，表明BK对MC3T3-E1细胞的刺激通过涉及Ca2+和蛋白激酶C的机制激活磷脂酶A2以释放花生四烯酸。
