MOLECULAR AND FUNCTIOINAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
基本信息
- 批准号:6353814
- 负责人:
- 金额:$ 3.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-09-15 至 2004-03-31
- 项目状态:已结题
- 来源:
- 关键词:adenosine triphosphate crosslink density gradient ultracentrifugation gel filtration chromatography immunoprecipitation molecular assembly /self assembly neural transmission neurotransmitter receptor protein structure function purinergic receptor receptor binding receptor expression recombinant proteins site directed mutagenesis tissue /cell culture
项目摘要
Evidence accumulated over the past three decades supports the role of adenosine-tripphosphate (ATP) as a neurotransmitter/neuromodulator in many adrenergic, cholinergic and non-adrenergic/non/cholinergic pathways. Its role as a chemical mediator of intercellular communication has been established in tissues such as the central and peripheral nervous systems, endocrine glands, heart and smooth muscle. However, the mechanisms which mediate ATP's role as a chemical signal is poorly understood. A primary reason for this is the presence of multiple receptor subtypes in most tissues coupled with a lack of subtype-selective agonists and antagonists. Additionally, in some tissues there are high levels of cell-surface enzymes (ecto-ATPases) that can quickly degrade many of the ATP analogues used for receptor classification, resulting in further complications. In order to clearly understand the role of ATP-mediated transmission, it is essential to define the pharmacological and physiological properties of ATP receptors. Currently, ATP receptors fall into one of two classifications, P2Y and P2X receptors. The focus of this grant are the ATP receptors which belong to the P2X category. These receptors are ligand-gated channels that are permeable not only to monovalent cations such as Na+ and K+, but also to Ca2+. In this project, we will circumvent the difficulties associated with investigating multiple receptor subtypes in their native settings through the use of recombinant receptor expression in mammalian cells. This approach allows for the expression of individual receptor subtypes in a controlled environment, thus permitting detailed characterization of the basic properties of a receptor subunit. We have embarked on the investigation of P2X receptors at the molecular and functional level using a compare and contrast methodology. In this study we will elucidate the stoichiometry of receptor assemblies, elucidate the domains involved in subunit interactions and identify amino acid residues that participate in agonist (binding and gating of the channel. These experiments will provide essential information regarding P2X receptor function and the role of ATP as a neurotransmitter in the central and peripheral nervous systems. The overall goal of this project is to provide a clearer understanding of the pharmacological and physiological properties associated with specific P2X receptor subtypes.
过去三十年积累的证据支持三磷酸腺苷(ATP)在许多肾上腺素能、胆碱能和非肾上腺素/非/胆碱能途径中作为神经递质/神经调节剂的作用。在中枢和外周神经系统、内分泌腺、心脏和平滑肌等组织中,已经确立了它作为细胞间通讯的化学媒介的作用。然而,对三磷酸腺苷作为化学信号的调节机制却知之甚少。其主要原因是在大多数组织中存在多种受体亚型,同时缺乏亚型选择性激动剂和拮抗剂。此外,在一些组织中存在高水平的细胞表面酶(胞外-ATPase),可以迅速降解许多用于受体分类的ATP类似物,导致进一步的并发症。为了清楚地了解三磷酸腺苷介导的信息传递的作用,有必要明确三磷酸腺苷受体的药理和生理特性。目前,ATP受体分为两类,即P2Y和P2X受体。这项资助的重点是属于P2X类别的ATP受体。这些受体是配体门控通道,不仅对单价阳离子如Na+和K+具有通透性,而且对钙离子也具有通透性。在这个项目中,我们将通过在哺乳动物细胞中使用重组受体表达来绕过与研究多种受体亚型在其天然环境中相关的困难。这种方法允许在受控环境中表达单个受体亚型,从而允许详细描述受体亚单位的基本特性。我们已经开始使用比较和对比的方法在分子和功能水平上对P2X受体进行研究。在这项研究中,我们将阐明受体组件的化学计量学,阐明亚基相互作用中涉及的结构域,并确定参与激动剂(结合和门控通道)的氨基酸残基。这些实验将提供关于P2X受体功能和ATP作为神经递质在中枢和外周神经系统中的作用的基本信息。该项目的总体目标是更清楚地了解与特定的P2X受体亚型相关的药理和生理特性。
项目成果
期刊论文数量(0)
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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MARK M VOIGT其他文献
MARK M VOIGT的其他文献
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Neural Circuitry in the Developing Zebrafish Spinal Cord
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MOLECULAR AND FUNCTIONAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
- 批准号:
6539891 - 财政年份:1996
- 资助金额:
$ 3.7万 - 项目类别:
MOLECULAR AND FUNCTIONAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
- 批准号:
6639507 - 财政年份:1996
- 资助金额:
$ 3.7万 - 项目类别:
MOLECULAR AND FUNCTIONAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
- 批准号:
2460658 - 财政年份:1996
- 资助金额:
$ 3.7万 - 项目类别:
MOLECULAR AND FUNCTIONAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
- 批准号:
2274802 - 财政年份:1996
- 资助金额:
$ 3.7万 - 项目类别:
MOLECULAR AND FUNCTIOINAL ANALYSIS OF ATP RECEPTORS
ATP 受体的分子和功能分析
- 批准号:
6129381 - 财政年份:1996
- 资助金额:
$ 3.7万 - 项目类别:
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