PULMONARY C-NEURON HYPERSENSITIVITY:CELLULAR MECHANISMS

肺 C 神经元过敏：细胞机制

• 批准号: 6879739
• 负责人: LU-YUAN LEE
• 金额: $ 28.96万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-08-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6879739
• 关键词: C fiber; biological signal transduction; capsaicin; chemical structure function; cyclic AMP; delayed hypersensitivity; electrophysiology; inflammation; laboratory rat; mucosa; neurons; ozone; prostaglandin E; prostaglandin endoperoxide synthase; prostaglandin receptor; protein kinase A; protein metabolism; protein structure function; respiratory airway pressure; respiratory epithelium; respiratory hypersensitivity; sodium channel; tissue /cell culture; voltage /patch clamp

DESCRIPTION (provided by applicant): The long-range goal of this research project is to understand the neurogenic mechanisms underlying the bronchial hyperreactivity caused by inflammation of airway mucosa. Increasing evidence suggests an involvement of hypersensitivity of bronchopulmonary C-fiber afferents in the manifestation of bronchial hyper-reactivity induced by airway epithelial injury. The primary objective of this proposal is to investigate the role of endogenous prostaglandin E2 (PGE2), a potent autacoid, in the sensitization of bronchopulmonary C fibers caused by airway mucosal inflammation, and to elucidate the cellular mechanisms involved in this action. PGE2 is locally synthesized and releases from airway epithelium during various inflammatory reactions, and our recent studies have demonstrated a sensitizing effect of exogenous PGE2 on the pulmonary C fibers. The central hypothesis of this study is that endogenous PGE2 increases the sensitivity of the pulmonary C-fiber endings by activating EP2 and/or EP4 prostanoid receptors; activation of these EP receptors enhances the neuronal excitability by activating the cyclic AMP/protein kinase A signaling pathway that leads to modulation of the function of tetrodotoxin-resistant sodium channel. Proposed experiments will be carried out to test these hypotheses in rats using both in vivo (single-fiber recording) and in vitro (whole-cell patch-clamp recording) preparations; the latter will be performed in isolated nodose and jugular ganglion neurons innervating the lung and airways. The results obtained from this study should provide crucial information for gaining new insight into the signaling transduction mechanisms underlying the PGE2-induced sensitization of pulmonary C neurons. This information may, therefore, help to develop new therapeutic strategies for alleviating the symptoms of bronchial hyperreactivity associated with airway mucosal inflammation.

描述（由申请人提供）：这项研究的远程目标 项目是要了解支气管的基础神经源机制 气道粘膜炎症引起的过度反应性。越来越多的证据 提示支气管肺C纤维超敏反应参与 气道引起的支气管超反应性表现的传入 上皮损伤。该提议的主要目的是调查 内源性前列腺素E2（PGE2）的作用，一种有效的自动肌，在 气道粘膜引起的支气管肺C纤维的敏化 炎症，并阐明该动作所涉及的细胞机制。 PGE2是局部合成的，并在各种过程中从气道上皮释放 炎症反应，我们最近的研究表明了敏感性 外源PGE2对肺C纤维的影响。中心假设 这项研究是内源性PGE2提高了肺的敏感性 通过激活EP2和/或EP4前列腺素受体来结尾；激活 在这些EP受体中，通过激活来增强神经元兴奋性 环状AMP/蛋白激酶A信号通路，导致调节 四毒素耐钠通道的功能。建议的实验将是 使用体内（单纤维）在大鼠中测试这些假设 记录）和体外（全细胞斑块钳记录）制剂；这 后者将以孤立的结节和颈神经元神经元进行 支配肺和气道。从这项研究获得的结果应该 提供至关重要的信息，以获得有关信号的新见解 PGE2诱导的肺敏化的基础的转导机制 C神经元。因此，此信息可能有助于开发新的治疗性 减轻相关支气管过度反应性症状的策略 气道粘膜炎症。

项目成果

Sensitizing effects of chronic exposure and acute inhalation of ovalbumin aerosol on pulmonary C fibers in rats.

• DOI: 10.1152/japplphysiol.01367.2007
• 发表时间: 2008-07
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: Guangfan Zhang;R. Lin;M. Wiggers;Lu-Yuan Lee

Calcium transient evoked by nicotine in isolated rat vagal pulmonary sensory neurons.

尼古丁在离体大鼠迷走肺感觉神经元中引起的钙瞬变。

• DOI: 10.1152/ajplung.00182.2006
• 发表时间: 2007
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: Xu,Jennings;Yang,Wenbin;Zhang,Guangfan;Gu,Qihai;Lee,Lu-Yuan
• 通讯作者: Lee,Lu-Yuan

Breathing hot humid air induces airway irritation and cough in patients with allergic rhinitis.

• DOI: 10.1016/j.resp.2014.03.013
• 发表时间: 2014-07-01
• 期刊: RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
• 影响因子: 2.3
• 作者: Khosravi, Mehdi;Collins, Paul B.;Lin, Ruei-Lung;Hayes, Don, Jr.;Smith, Jaclyn A.;Lee, Lu-Yuan
• 通讯作者: Lee, Lu-Yuan

A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents.

• DOI: 10.1152/japplphysiol.00805.2014
• 发表时间: 2015-02
• 期刊: Journal of applied physiology
• 影响因子: 3.3
• 作者: Yu-Jung Lin;R. Lin;T. Ruan;M. Khosravi;Lu-Yuan Lee