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首页> 外文期刊>The European Journal of Neuroscience >Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter.
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Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter.

机译:在缺乏5-HT转运蛋白的基因敲除小鼠中,血清素5-HT1A和5-HT1B受体的表达和功能发生了改变。

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By taking up serotonin (5-hydroxytryptamine, 5-HT) released in the extracellular space, the 5-HT transporter (5-HTT) regulates central 5-HT neurotransmission. Possible adaptive changes in 5-HT neurotransmission in knock-out mice that do not express the 5-HT transporter were investigated with special focus on 5-HT1A and 5-HT1B receptors. Specific labelling with radioligands and antibodies, and competitive RT-PCR, showed that 5-HT1A receptor protein and mRNA levels were significantly decreased in the dorsal raphe nucleus (DRN), increased in the hippocampus and unchanged in other forebrain areas of 5-HTT-/- vs. 5-HTT+/+ mice. Such regional differences also concerned 5-HT1B receptors because a decrease in their density was found in the substantia nigra (-30%) but not the globus pallidus of mutant mice. Intermediate changes were noted in 5-HTT+/- mice compared with 5-HTT+/+ and 5-HTT-/- animals. Quantification of [35S]GTP-gamma-S binding evoked by potent 5-HT1 receptor agonists confirmed such changes as a decrease in this parameter was noted in the DRN (-66%) and the substantia nigra (-30%) but not other brain areas in 5-HTT-/- vs. 5-HTT+/+ mice. As expected from actions mediated by functional 5-HT1A and 5-HT1B autoreceptors, a decrease in brain 5-HT turnover rate after i.p. administration of ipsapirone (a 5-HT1A agonist), and an increased 5-HT outflow in the substantia nigra upon local application of GR 127935 (a 5-HT1B/1D antagonist) were observed in 5-HTT+/+ mice. Such effects were not detected in 5-HTT-/- mice, further confirming the occurrence of marked alterations of 5-HT1A and 5-HT1B autoreceptors in these animals.
机译:通过吸收5-羟色胺(5-羟色胺,5-HT)释放到细胞外空间,5-HT转运蛋白(5-HTT)调节中枢5-HT神经传递。研究了不表达5-HT转运蛋白的基因敲除小鼠中5-HT神经传递的可能适应性变化,特别关注了5-HT1A和5-HT1B受体。放射性配体和抗体的特异性标记以及竞争性RT-PCR表明,背根核(DRN)中的5-HT1A受体蛋白和mRNA水平显着降低,海马体中的5-HT1A受体蛋白和mRNA水平显着升高,而其他前脑区域中的5-HTT-与5-HTT + / +小鼠相比。这种区域差异也与5-HT1B受体有关,因为在黑质(-30%)中发现了它们密度的降低,而在突变小鼠的苍白球中却没有发现。与5-HTT + / +和5-HTT-/-动物相比,在5-HTT +/-小鼠中注意到中间变化。强大的5-HT1受体激动剂引起的[35S]GTP-γ-S结合的定量证实了这样的变化,如DRN(-66%)和黑质(-30%)中注意到该参数降低,但其他没有5-HTT-/-与5-HTT + / +小鼠的大脑区域。正如功能性5-HT1A和5-HT1B自身受体介导的作用所预期的那样,腹腔注射后脑部5-HT转换率降低。在5-HTT + / +小鼠中观察到,在局部应用GR 127935(5-HT1B / 1D拮抗剂)后,ipsapirone(5-HT1A激动剂)的给药和黑质中5-HT流出增加。在5-HTT-/-小鼠中未检测到这种作用,进一步证实了这些动物中5-HT1A和5-HT1B自体受体发生明显改变。

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