CHEMOTRANSDUCTION IN THE CAROTID BODY

颈动脉体内的化学转导

• 批准号: 2226977
• 负责人: ROBERT Schaefer FITZGERALD
• 金额: $ 27.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2226977
• 关键词: acidosis; biological signal transduction; carotid body; cats; cholinergic agents; dopamine; dopamine receptor; high performance liquid chromatography; hypercapnia; hypoxia; immunocytochemistry; laboratory rabbit; membrane potentials; muscarinic receptor; neural transmission; neurochemistry; neuropeptide receptor; neuropharmacology; neurotransmitters; nicotinic receptors; perfusion; potassium channel; voltage /patch clamp

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The broad objectives of this application are to gain deeper insight into the mechanisms operating during the carotid body's (cb) chemotransduction of hypoxia, hypercapnia, and acidosis into increased neural activity recordable in the carotid sinus nerve. On the assumption that (a) the essential chemotransductive unit consists of the Type I cell and the apposed neuron, (b) that hypoxia depolarizes the Type I cell provoking the release of neuroagent(s) which bind to a receptor(s) on the apposed neuron, and (c) this initiates processes responsible for the recordable action potentials in the carotid sinus nerve, two questions can be asked: (1) How is the Type I cell depolarized so as to release the neuroagents? (2) What are the essential excitatory and inhibitory neuroagents in the cat and how are they managed? This application addresses the second question.Five areas of research are proposed, each containing focused hypotheses to be tested: (1) Analyze the venous effluent from the in situ cat carotid body for neurotransmitters (Are those released during hypercapnia the same as those released during hypoxia?); (2) Identify the cb's excitatory and inhibitory neurotransmitters and their pharmacological interaction (Does the cb respond more to hypoxia in the presence of an M2 receptor blocker?); (3) Determine the presence and location of specific neurotransmitter receptors (Is there a neuronal nicotinic receptor on the dendrite apposed Type I cell?); (4) determine the effect of cholinergic agonists and dopamine on membrane potential and potassium channels of the Type I cells (What does ACh do to the calcium-activated potassium current?); (5) Repeat the studies of (2) in the rabbit which responds differently from the cat. Techniques include neural recording, HPLC analysis, immunocytochemistry, and patch clamping cultured Type I cells. Better knowledge of how the cb works could perhaps allow the creation of an agent to temporarily block input from the cb.

描述：（改编自申请人的摘要和具体目标。） 此应用程序的主要目标是更深入地了解 颈动脉体（cb）的作用机制 低氧、高碳酸血症和酸中毒的化学转导增加 在颈动脉窦神经中可记录的神经活动。 上 假设（a）基本化学转导单位由 I型细胞和并列的神经元，（B）缺氧去极化 I型细胞引起神经剂的释放，所述神经剂结合至 受体（s）对并列的神经元，和（c）这引发的过程 负责颈动脉窦中可记录的动作电位 神经，两个问题可以问：（1）如何是I型细胞 去极化以释放神经毒剂 (2)什么是基本的 兴奋性和抑制性神经剂在猫和他们是如何 管理？ 本申请解决了第二个问题。 提出了一些研究，每个研究都包含有待检验的重点假设： (1)分析猫颈动脉体的静脉流出物， 神经递质（高碳酸血症期间释放的神经递质是否与 缺氧时释放的？）; (2)识别cb的兴奋性和 抑制性神经递质及其药理学相互作用（Does 在M2受体存在的情况下，cb对缺氧的反应更大 blocker？）; (3)确定特定的 神经递质受体（是否有神经元烟碱受体， 树突并列的I型细胞？）; (4)确定影响的 胆碱能激动剂和多巴胺对膜电位和钾离子的影响 I型细胞的通道（ACh对钙激活的 钾电流？）; (5)在家兔中重复（2）的研究， 反应与猫不同。技术包括神经记录， HPLC分析、免疫细胞化学和膜片钳培养I型 细胞 更好地了解cb的工作原理， 创建代理以暂时阻止来自CB的输入。