Abstract
Objective
To investigate the underlying mechanism for the selective modulation of the permeability of blood-tumor barrier (BTB) by small dose of bradykinin (BK).
Methods
C6 glioma cells were treated with BK, and changes of intracellular nitric oxide (NO) and intracellular calcium level were measured with fluorescent spectrophotometer.
Results
The initial application of BK easily triggered extracellular calcium influx, which resulted in intracellular calcium store release in C6 glioma cells. The above mechanism was also named ryanodine mediated calcium induced calcium release (CICR). We also detected a long-lasting intracellular NO elevation in C6 glioma cells upon BK treatment. Further study showed that ryanodine mediated CICR contributed greatly to the secondary NO elevation induced by BK treatment.
Conclusion
These results suggested that BK triggered CICR in C6 glioma cells and the associated NO generation might be the underlying mechanism for the selective modulation of BTB permeability by BK.
Keywords: bradykinin, blood brain barrier, glioma
摘要
目的
探讨小剂量缓激肽选择性开放血肿瘤屏障的内在机制。
方法
通过免疫荧光探针实时测定缓激肽刺激前后C6胶质瘤细胞内的钙离子和一氧化氮 (nitric oxide, NO) 的变化。
结果
C6胶质瘤细胞上存在尼诺丁敏感受体, 小剂量缓激肽可以引起肿瘤细胞外的钙离子内流, 导致细胞内钙离子水平升高, 特别是首次刺激后, 细胞外钙离子内流可以选择性的引起 C6胶质瘤细胞内的钙库释放, 即 Ca2+ 内流诱发的 Ca2+ 释放 (calcium-induced calcium release, CICR)。 同时, 缓激肽刺激后, 在C6 胶质瘤细胞内存在 NO 的持续升高, 且NO 是继发于细胞内尼诺丁受体介导的CICR之后。
结论
小剂量缓激肽选择性触发C6胶质瘤细胞内钙库释放, 可能是小剂量缓激肽可以选择性开放血肿瘤屏障的原因。
关键词: 缓激肽, 血脑屏障, 胶质瘤
References
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