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GABAA Receptors and Tonic Inhibition: Towards an Improved Understanding of Agonist Binding and in vivo Expression of the Extrasynaptic alpha 4beta3delta Subtype.

机译:GABAA受体和补品抑制:促进对激动剂结合和突触外α4beta3delta亚型的体内表达的更好的了解。

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摘要

The GABAA receptor is the major inhibitory neurotransmitter receptor in the central nervous system. Receptors containing the delta subunit generate tonic inhibition due to their extrasynaptic expression, high affinity for gamma-aminobutyric acid (GABA), and slow densensitization kinetics. The present work had two goals: first, compare structural elements involved in agonist binding in the alpha1beta2gamma2 and alpha4beta3delta receptors, which are model synaptic and extrasynaptic receptor subtypes, respectively; second, develop an immunoassay using two-step fluorescence resonance energy transfer to detect the incorporation of three subunits into one receptor complex. The structural studies showed that the loop D region participates in agonist activity at both receptor subtypes, and that the agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) may function through a distinct subsite from that of GABA. Inadequate expression of the subunit constructs limited progress on the immunoassay, requiring more work to optimize the expression system before proceeding to proof-of-principle studies using two-step FRET.
机译:GABAA受体是中枢神经系统中主要的抑制性神经递质受体。含有δ亚基的受体由于其突触外表达,对γ-氨基丁酸(GABA)的高亲和力和缓慢的致敏动力学而产生了强直抑制作用。目前的工作有两个目标:首先,比较参与α1beta2gamma2和α4beta3delta受体激动剂结合的结构元件,它们分别是模型突触和突​​触外受体亚型。第二,开发一种利用两步荧光共振能量转移的免疫测定方法,以检测将三个亚基掺入一个受体复合物中。结构研究表明,环D区在两种受体亚型中均参与激动剂活性,并且激动剂4,5,6,7-四氢异恶唑并[5,4-c]吡啶-3-醇(THIP)可能通过与GABA不同的子站点。亚基的表达不足会在免疫测定中取得有限的进展,需要更多的工作来优化表达系统,然后再进行使用两步FRET的原理验证研究。

著录项

  • 作者

    Nilsson, Benjamin Gene.;

  • 作者单位

    University of Alberta (Canada).;

  • 授予单位 University of Alberta (Canada).;
  • 学科 Pharmacology.
  • 学位 M.S.
  • 年度 2013
  • 页码 167 p.
  • 总页数 167
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 老年病学;
  • 关键词

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