δ阿片受体的表达和激活对谷氨酸转运蛋白EAAC1的调节

发布时间：2018-01-02 19:23

本文关键词：δ阿片受体的表达和激活对谷氨酸转运蛋白EAAC1的调节　出处：《中国科学院研究生院（上海生命科学研究院）》2006年博士论文　论文类型：学位论文

【摘要】：谷氨酸转运蛋白在调节突触间隙内的谷氨酸的时空分布上起重要的作用,它防止由于胞外过高的谷氨酸浓度而给细胞带来的毒害作用。兴奋性氨基酸转运蛋白EAAC1是神经元特异性的,它参与调节突触间隙的谷氨酸浓度。阿片受体在大脑中参与谷氨酸能神经系统的调节,但是具体的机制仍需要进行进一步研究。本文报道了在非洲爪蟾卵母细胞中delta阿片受体(DOR)与EAAC1的共表达可以下调EAAC1的功能,而mu阿片受体的共表达并不影响EAAC1的功能。EAAC1由于DOR的表达而导致的下降功能可通过DPDPE激活DOR受体而得到抵消。用生物素标记膜上受体的实验结果显示这种DOR对EAAC1功能的调节并不改变胞内和膜上的EAAC1表达量。从卵母细胞和大鼠海马神经细胞得到的免疫共沉淀和免疫荧光的结果均显示EAAC1和DOR两种蛋白存在共定位,这表明二者之间存在直接的相互作用。与EAAC1功能实验一致的是DPDPE激活DOR会减弱他们之间的相互作用。我们的结果提示delta阿片受体可以通过蛋白-蛋白间的相互作用来调节EAAC1的功能,而DOR的激活可以释放这种相互作用导致的抑制作用。我们认为这个机制可能在阿片处理后的谷氨酸能神经系统的调节中发挥重要作用。
[Abstract]:Glutamate transporter plays an important role in regulating the spatial and temporal distribution of glutamate in synaptic space. The excitatory amino acid transporter (EAAC1) is neuron-specific. It is involved in regulating glutamate concentrations in the synaptic space. Opioid receptors are involved in the regulation of the glutamate nervous system in the brain. However, the specific mechanism still needs to be further studied. It is reported that the co-expression of delta opioid receptor and EAAC1 in Xenopus oocytes can down-regulate the function of EAAC1. But the co-expression of mu opioid receptor does not affect the function of EAAC1. The decline of EAAC1 caused by the expression of DOR can be counteracted by the activation of DOR receptor by DPDPE. The results of labeling the receptors on the membrane showed that the regulation of DOR on the function of EAAC1 did not change the expression of EAAC1 in cells and membranes. Immunoprecipitation from oocytes and rat hippocampal neurons. And the results of immunofluorescence showed that EAAC1 and DOR existed colocalization. This indicates that there is a direct interaction between the two, and it is consistent with the EAAC1 functional experiment that the activation of DOR by DPDPE weakens the interaction between them. Our results suggest that delta opioid receptors can regulate the function of EAAC1 through protein-protein interaction. The activation of DOR can release the inhibition resulting from this interaction. We believe that this mechanism may play an important role in the regulation of glutamate nervous system after opioid treatment.
【学位授予单位】：中国科学院研究生院（上海生命科学研究院）
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R33

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