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

突触刺激激活了突触后神经元核内特定的基因表达程序，这对神经元细胞的长期适应性反应至关重要。MAP激酶被认为在神经递质释放引发的信号转导中具有重要作用。通过L型钙通道的钙内流激活MAP激酶，并且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，本研究检测了麻醉剂对去极化诱导的PC 12细胞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30 μ M地布卡因或200 μ M丁卡因的影响。2.地布卡因、丁卡因和丙泊酚剂量依赖性地抑制KCl诱导的PC 12细胞核cFos表达。CFO ...更多信息 浓度分别为30、50和50 μ M的地布卡因、丁卡因和丙泊酚可抑制50 mM KCl诱导的s表达。KCl诱导的cFos表达被3 mM EDTA、10 μ M硝苯地平阻断，但不被3 μ M ω-芋螺毒素阻断，表明KCl诱导的cFos表达依赖于通过L-型钙通道的钙内流。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-型钙通道的浓度相容。MEK（MAP kinase kinase，MAP激酶）激活剂PD 9805也能抑制KC 1诱导的cFos表达。3.地布卡因和丁卡因呈剂量依赖性抑制KC 1诱导的MAP激酶激活。10 μ M地布卡因和50 μ M丁卡因均能抑制KCl诱导的MAP激酶激活，提示地布卡因和丁卡因可抑制L型钙通道和MAP激酶信号通路，从而抑制神经细胞核基因表达。目前认为异丙酚对MAP信号通路和基因表达具有相同的影响，本研究旨在探讨麻醉药对人中性粒细胞MAP激酶信号通路的影响。少

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