The effects of anesthetics on the signal transduction of neuronal cells and neutrophils.

麻醉剂对神经元细胞和中性粒细胞信号转导的影响。

• 批准号: 07671667
• 负责人: KANSHA Masumi
• 金额: $ 1.41万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671667/
• 关键词: Signal transduction; Anesthetics; PC12; cFos; 神経系細胞

Synaptic stimulation activates specific program of gene expression in the nucleus of postsynaptic neurons, which seems critical to long-term adaptive responses of neuronal cells. It has been thought that MAP kinase has an important role in transducing signals that are initiated by neurotransmitter release. Calcium influx through L-type calcium channels activates MAP kinase, and L-type calcium channels and MAP kinase are localized to postsynaptic structures in central nervous system. To elucidate the possibility that anesthetics affect the synaptic plasticity, I examined the effects of anesthetics on depolarization-induced MAP kinase activation and cFos expression in PC12 cells.1.Outgrowth of neurofilaments induced by nerve growth factor was not affected by 30muM dibucaine or 200 muM tetracaine. PC12 cells died in the presence of higher concentrations of these local anesthetics2.Dibucaine, tetracaine and propofol dose-dependently inhibited KC1-induced cFos expression in the nucleus. cFo … More s expression induced by 50 mM KC1 was suppressed by dibucain, tetracaine, and propofol at the concentrations of 30,50 and 50 muM,respectively. KC1-induced cFos expression was blocked by 3 mM EDTA,10 muM nifedipine but not by 3 muM omega-conotoxin, indicating that KC1-induced cFos expression depends on calcium influx through L-type calcium channels. The concentrations of dibucaine and tetracaine which blocked cFos expression were compatible with those which were reported to inhibit L-type calcium channels in spinal cord ganglion cells. KC1-induced cFos exppression was also inhibited by PD9805, a MEK (MAP kinase kinase) inhibitor.3.Dibucaine and tetracaine inhibited KC1-induced MAP kinase activation in dose-dependent manner. KC1-induced MAP kinase activation was suppressed by 10 muM dibucaine and 50 muM tetracaine.These findings suggest that dibucaine and tetracaine suppress L-type calcium channels and MAP kinase signaling pathway, resulting inhibition of gene expression in the nucleus of neuronal cells. It is supposed that propofol has the same effect on MAP signaling pathway and gene expression.Now, I examine the effects of anesthetics on MAP kinase signaling pathway in human neutrophils. Less

突触刺激激活突触后神经元细胞核中特定的基因表达程序，这似乎对神经元细胞的长期适应性反应至关重要。人们认为 MAP 激酶在神经递质释放引发的信号转导中具有重要作用。钙通过 L 型钙通道流入激活 MAP 激酶，L 型钙通道和 MAP 激酶定位于中枢神经系统的突触后结构。为了阐明麻醉剂影响突触可塑性的可能性，我研究了麻醉剂对PC12细胞中去极化诱导的MAP激酶激活和cFos表达的影响。1.神经生长因子诱导的神经丝生长不受30μM地布卡因或200μM丁卡因的影响。 PC12 细胞在较高浓度的局部麻醉剂存在下死亡2。地布卡因、丁卡因和异丙酚剂量依赖性地抑制 KC1 诱导的细胞核内 cFos 表达。 50 mM KC1 诱导的 cFo … More s 表达分别被浓度为 30,50 和 50 muM 的地布卡因、丁卡因和异丙酚抑制。 KC1 诱导的 cFos 表达被 3 mM EDTA、10 muM 硝苯地平阻断，但不被 3 mM omega-芋螺毒素阻断，表明 KC1 诱导的 cFos 表达依赖于通过 L 型钙通道的钙流入。阻断 cFos 表达的地布卡因和丁卡因的浓度与报道的抑制脊髓神经节细胞中 L 型钙通道的浓度相一致。 KC1诱导的cFos表达也被MEK（MAP激酶激酶）抑制剂PD9805抑制。3.地布卡因和丁卡因以剂量依赖性方式抑制KC1诱导的MAP激酶激活。 KC1诱导的MAP激酶活化被10μM丁卡因和50μM丁卡因抑制。这些研究结果表明，丁卡因和丁卡因抑制L型钙通道和MAP激酶信号通路，从而抑制神经元细胞核中的基因表达。推测异丙酚对MAP信号通路和基因表达具有相同的作用。现在，我研究麻醉药对人中性粒细胞MAP激酶信号通路的影响。较少的