Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Cancer Cell Int. 2010 Sep 27;10:35. doi: 10.1186/1475-2867-10-35.
Purinergic receptor-mediated signaling plays an important role in the function of glial cells, including glial tumor cells. Bradykinin is also an important paracrine mediator which is highly expressed in brain tumors and may correlate with their pathological grade. Interaction between bradykinin and purinergic signaling may therefore be involved in the regulation of glial tumor cells.
We examined the effect of bradykinin on glial purinergic signaling in an immortalized glioma cell line. Confocal calcium imaging revealed that ATP evokes an increase in [Ca2+]i in the U87 human astrocytoma cell line. This response was reduced with repetitive application of ATP, likely due to receptor desensitization. However exposure to bradykinin increased the Ca2+ response to a second application of ATP, consistent with increased resensitization. The bradykinin effect on resensitization was similar in the absence of extracellular Ca2+ or in the presence of the PKC activator PMA, but was inhibited by the protein phosphatase inhibitor okadaic acid and the PI3K inhibitor LY294002.
Modulation of protein phosphatases and the PI3K pathway may represent a mechanism by which bradykinin potentiates purinergic signaling in glial cells.
嘌呤能受体介导的信号转导在神经胶质细胞（包括神经胶质瘤细胞）的功能中发挥着重要作用。缓激肽也是一种重要的旁分泌介质，在脑肿瘤中高度表达，可能与肿瘤的病理分级相关。缓激肽与嘌呤能信号转导的相互作用可能参与了神经胶质肿瘤细胞的调控。
我们研究了缓激肽对永生性神经胶质瘤细胞系中神经胶质嘌呤能信号转导的影响。共聚焦钙离子成像显示，ATP 可引发 U87 人星形细胞瘤系中 [Ca2+]i 的增加。这种反应在 ATP 的重复应用中减少，可能是由于受体脱敏所致。然而，缓激肽的暴露增加了对第二次 ATP 应用的 Ca2+反应，与增强的再敏化一致。缓激肽对再敏化的影响在不存在细胞外 Ca2+或存在 PKC 激活剂 PMA 的情况下相似，但被蛋白磷酸酶抑制剂 okadaic acid 和 PI3K 抑制剂 LY294002 抑制。
蛋白磷酸酶和 PI3K 通路的调节可能是缓激肽增强神经胶质细胞中嘌呤能信号转导的一种机制。
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