Noncompetitive Inhibition of Acetylcholine Receptor

乙酰胆碱受体的非竞争性抑制

• 批准号: 9215105
• 负责人: David Johnson
• 金额: $ 23.65万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9215105&HistoricalAwards=false
• 关键词: Noncompetitive; Inhibition; Acetylcholine; Receptor

Information moves from the brain to muscle through neurons. The transfer of information between neuron and muscle involves the release of a chemical called acetylcholine from the neuron and the diffusion of acetylcholine to the muscle. Acetylcholine binds to proteins called acetylcholine receptors on the surface of muscle cells, transiently opening small ion channels in the cell membrane. These channel openings initiate muscle contraction. The electric organs in invertebrates are extraordinarily rich in these acetylcholine receptors and, consequently, are the model system used to study the molecular basis of action of acetylcholine or any other agent that acts on acetylcholine receptors. Over the last twelve years, using quantitative fluorescence spectroscopy, Dr. Johnson has developed a unique approach for the study of structural features of intact ligand receptors. He will continue to use this approach to delineate the sites of binding of inhibitors of the acetylcholine receptor. Specifically, he will localize the sites of binding of two noncompetitive inhibitors of the acetylcholine with respect to the surface and side of the cell membrane, as well as their orientation when bound to the receptor. This information will significantly contribute to the development of a molecular understanding of the actions of chemicals on this receptor. Moreover, concepts and experimental approaches developed in the study of the acetylcholine receptor should easily be exportable to the examination of other neurotransmitter and hormone receptors.

信息通过神经元从大脑传递到肌肉。神经元和肌肉之间的信息传递涉及到从神经元释放一种叫做乙酰胆碱的化学物质，并将乙酰胆碱扩散到肌肉。乙酰胆碱与肌肉细胞表面的一种叫做乙酰胆碱受体的蛋白质结合，在细胞膜上瞬间打开小的离子通道。这些通道开口引起肌肉收缩。无脊椎动物的电器官非常富含这些乙酰胆碱受体，因此，它是用于研究乙酰胆碱或任何其他作用于乙酰胆碱受体的物质的分子基础的模型系统。在过去的12年里，约翰逊博士使用定量荧光光谱法开发了一种独特的方法来研究完整配体受体的结构特征。他将继续使用这种方法来描述乙酰胆碱受体抑制剂的结合位点。具体来说，他将定位两种乙酰胆碱非竞争性抑制剂在细胞膜表面和侧面的结合位点，以及它们与受体结合时的取向。这一信息将极大地促进对化学物质对该受体作用的分子理解的发展。此外，在乙酰胆碱受体研究中发展起来的概念和实验方法应该很容易输出到其他神经递质和激素受体的检查中。