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

突触刺激激活突触后神经元核内基因表达的特定程序，这似乎对神经元细胞的长期适应性反应至关重要。目前认为MAP激酶在神经递质释放所启动的信号转导中起着重要作用。钙离子通过L型钙通道内流激活MAPK，L型钙通道和MAPK定位于中枢神经系统的突触后结构。为了阐明麻醉药影响突触可塑性的可能性，我观察了麻醉药对去极化诱导的PC12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细丝生长不受30 mM地布卡因或200 mU丁卡因影响。在高浓度局麻药存在下，PC12细胞死亡。丁卡因、丁卡因和异丙酚可剂量依赖地抑制Kc1诱导的CFos在核内的表达。首席财务官…浓度分别为30、50和50 mM的丁卡因、丁卡因和异丙酚可抑制50 mM Kc1诱导的更多S的表达。3 mM EDTA、10 mU硝苯地平可阻断Kc1诱导的CFos的表达，而3 mM的欧米茄毒素不能阻断Kc1诱导的CFos的表达，提示Kc1诱导的CFos的表达依赖于L型钙通道的钙内流。阻断CFos表达的地布卡因和丁卡因浓度与文献报道的抑制脊神经节细胞L型钙通道的浓度一致。MEK抑制剂PD9805也能抑制Kc1诱导的CFos表达。3.地布卡因和丁卡因剂量依赖地抑制Kc1诱导的MAPK激活。10 mU的地布卡因和50 mU的丁卡因均可抑制Kc1诱导的MAPK激活，提示地布卡因和丁卡因可抑制L钙通道和MAPK信号转导通路，从而抑制神经元细胞核的基因表达。据推测，异丙酚对MAP信号通路和基因表达具有相同的影响。现在，我检测了麻醉药对人中性粒细胞MAP信号通路的影响。较少

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