Slow Excitatory Phenomena - Interaction of Excitatory Amino Acids and Neuropeptides

慢兴奋现象 - 兴奋性氨基酸和神经肽的相互作用

基本信息

  • 批准号:
    9209462
  • 负责人:
  • 金额:
    $ 19.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Continuing Grant
  • 财政年份:
    1992
  • 资助国家:
    美国
  • 起止时间:
    1992-09-01 至 1996-02-29
  • 项目状态:
    已结题

项目摘要

The perception of pain requires excitatory synaptic transmission from primary afferent sensory fibers to secondary projection neurons in the dorsal horn of the spinal cord. Two groups of neurotransmitter candidates are thought to mediate this initial excitatory step in the pain pathway: one being excitatory amino acids (EAA: glutamate, asparate), and another are peptides (including tachykinins such as substance P and neurokinin A). These peptides may be colocalized with an excitatory amino acid(s) in the same neurons. Chemical signal transfer via such neurons presents new aspects and complexities of presynaptic (synaptic efficacy) and postsynaptic (membrane excitability) regulation which have not previously been considered and may have important implications for the performance of the somatosensory, especially of pain pathways. Dr. Randic has recently found that substance P and excitatory amino acids interact to produce neurophysiological signs of hyperalgesia i.e. a prolonged enhancement of responses to excitatory manipulation. However, the sites and the molecular mechanisms by which the peptide signals produce enhanced EAA responses have yet to be elucidated. Dr. Randic will examine the hypothesis that the activation of distinct neurokinin receptors causes modulation of the responses of freshly isolated spinal dorsal horn neurons to EAAs, especially to N-methyl-D-aspartic- acid (NMDA). To gain understanding of molecular mechanism(s) underlying interactions between EAAs, and tachykinins possible involvement of glycine allosteric site of NMDA receptor channel complex, guanine nucleotide-binding proteins (G-proteins) or change in Ca++-sensitive second messenger systems, will be investigated. Whole-cell voltage-clamp recording of EAA responses will be utilized in this study. Delineating the cellular mechanism(s) of peptide actions on dorsal horn neurons is an important step toward understanding anatomical and neurochemical organization of the spinal dorsal horn.***//
疼痛的感知需要兴奋性突触传递 从初级传入感觉纤维到次级投射 脊髓背角的神经元。 两组 神经递质候选者被认为是介导这种初始的 疼痛通路中的兴奋性步骤:一个是兴奋性氨基 酸(EAA:谷氨酸,谷氨酸),另一种是肽 (包括速激肽,如P物质和神经激肽A)。 这些肽可以与兴奋性氨基酸共定位, 相同的神经元。 通过这种神经元的化学信号传递 提出了新的方面和复杂性的突触前(突触 功效)和突触后(膜兴奋性)调节, 以前没有考虑过,可能具有重要意义 对躯体感觉功能的影响,特别是 疼痛路径。 兰迪奇博士最近发现P物质 和兴奋性氨基酸相互作用, 痛觉过敏的迹象,即对 兴奋性操纵 然而,这些位点和分子 肽信号产生增强的EAA的机制 答复尚待阐明。 兰迪奇医生会检查 不同神经激肽受体的激活 引起新鲜分离的脊髓的反应的调制 背角神经元对EAA的反应,尤其是对N-甲基-D-天冬氨酸- 酸(NMDA)。 了解分子机制 EAA和速激肽之间可能存在潜在的相互作用 NMDA受体通道甘氨酸变构位点参与 复合物,鸟嘌呤核苷酸结合蛋白(G蛋白)或变化 在Ca++敏感的第二信使系统,将进行调查。 EAA反应的全细胞电压钳记录将在 在这项研究中使用。 描述细胞机制 肽对背角神经元的作用是向 了解大脑皮层的解剖学和神经化学组织 脊髓背角 *//

项目成果

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专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Mirjana Randic其他文献

Ascending spinal axons that signal the position of the hindlimbs under static conditions: Location and receptor input
在静态条件下发出后肢位置信号的上升脊髓轴突:位置和受体输入
  • DOI:
    10.1007/bf00235814
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    2
  • 作者:
    J. Wei;J. Simon;Mirjana Randic;Paul R. Burgess
  • 通讯作者:
    Paul R. Burgess

Mirjana Randic的其他文献

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{{ truncateString('Mirjana Randic', 18)}}的其他基金

Involvement of Glutamate Metabotropic Receptors in Synaptic Plasticity in the Spinal Cord
谷氨酸代谢型受体参与脊髓突触可塑性
  • 批准号:
    0200051
  • 财政年份:
    2002
  • 资助金额:
    $ 19.08万
  • 项目类别:
    Continuing Grant
Role of Glutamate Metabotropic Receptors in Synaptic Function in the Spinal Cord
谷氨酸代谢型受体在脊髓突触功能中的作用
  • 批准号:
    9604654
  • 财政年份:
    1997
  • 资助金额:
    $ 19.08万
  • 项目类别:
    Continuing Grant
Spinal Excitatory Synaptic Transmission: Mediators, Modulators and Second Messengers
脊髓兴奋性突触传递:调解者、调节者和第二信使
  • 批准号:
    8812172
  • 财政年份:
    1989
  • 资助金额:
    $ 19.08万
  • 项目类别:
    Continuing Grant
Physiological and Pharmacological Studies of Peptides in theSpinal Dorsal Horn
脊髓背角肽的生理和药理研究
  • 批准号:
    8418042
  • 财政年份:
    1985
  • 资助金额:
    $ 19.08万
  • 项目类别:
    Continuing Grant
Substance P Excitatory Action on Spinal Sensory Neurons
P 物质对脊髓感觉神经元的兴奋作用
  • 批准号:
    7723871
  • 财政年份:
    1978
  • 资助金额:
    $ 19.08万
  • 项目类别:
    Continuing Grant

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