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Sensory C Fibers in the Upper Airways

上呼吸道的感觉 C 纤维

基本信息

批准号：
8121419
负责人：
Thomas Edward Taylor-Clark
金额：
$ 24.84万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-20 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8121419
关键词：
9-deoxy-delta-9-prostaglandin D2 Action Potentials Address Afferent Neurons Agonist Allergens Allergic Allergic inflammation Area Biological Bradycardia Bradykinin B2 Receptor Breathing Bronchial Spasm C Fiber Cardiac Cardiopulmonary Cavia Clinical Research Data Disease Environmental Irritants Esthesia Event G-Protein-Coupled Receptors Goals Health Histamine Hypotension In Situ Inflammatory Investigation Irritants Knowledge Label Lead Leukotriene D4 Ligands Mediating Mediator of activation protein Molecular Mucous Membrane Mucous body substance Nature Nerve Neurons Neurotransmitters Nociception Nociceptors Nose Operative Surgical Procedures Pattern Physiology Play Population Preparation Process Prostaglandin D2 Prostaglandins Receptor Activation Reflex action Regulation Research Role Sensory Signal Transduction Sneezing Stimulus Structure of mucous membrane of nose Symptoms TRP channel TRPV1 gene Techniques Tobacco smoke Trigeminal System afferent nerve allergic airway inflammation base capsaicin receptor career experience insight mast cell mustard oil neurochemistry neuronal excitability novel patch clamp pollutant receptor respiratory response skills

项目摘要

Activation of sensory nerves in the upper airways by allergic inflammation, surgical intervention, airborne pollutants and tobacco smoke initiates cardiopulmonary and upper airway reflexes. Reflexes and sensations include sneezing, itch, congestion, mucus secretion, bronchospasm, altered respiratory pattern, arterial hypotension and bradycardia. The specific nature of a given reflex response is likely due to the type of upper airway afferent nerve that is activated. However, progress in this area has been limited by a lack of information regarding upper airways sensory nerve subtypes and their mechanisms of activation. In Aim 1, we will address the novel hypothesis that there are two distinct chemosensitive (nociceptor C-fiber) sensory nerve subtypes innervating the upper airways based on activation profile, neurotransmitter content and the area ofthe mucosa they innervate. In Aims 2 and 3 we will study the activation of these subt3rpes by key stimulants of upper airways-mediated reflexes. Specifically, in Aim 2, we will address hypotheses relating to the role of transient receptor potential Al (TRPAl) in the activation of upper airways nociceptors. TRPAl receptors are activated by a wide range of exogenous substances including pollutants, foodstuffs and tobacco smoke constituents. TRPAl receptors are also targets for downstream signaling events following G-protein coupled receptor activation (e.g. bradykinin B2 receptors). In addition we present the novel hypothesis that TRPAl receptors are directly activated by the endogenously-produced prostanoid 15-deoxy-deltal2,14-prostaglandin J2, a metabolite of PGD2. In Aim 3 we will address the hypotheses that specific mast cell mediators effect upper airway nociceptor activity via 2 distinct mechanisms: "activation" and "altered excitability". We will also evaluate the mechanisms by which these events occur. We will use a combination of anatomical and electrophysiological techniques to address our hjT)Otheses.

通过空气传播的过敏性炎症、外科干预激活上呼吸道感觉神经污染物和烟草烟雾会引发心肺和上呼吸道反射。反射和感觉包括打喷嚏、瘙痒、充血、粘液分泌、支气管痉挛、呼吸模式改变、动脉低血压和心动过缓。一个给定的反射反应的特定性质可能是由于上丘脑的类型被激活的呼吸道传入神经。然而，由于缺乏信息，这一领域的进展受到限制。关于上呼吸道感觉神经亚型及其激活机制。在目标1中，我们将解决存在两种不同的化学敏感性(伤害性感受器C纤维)感觉神经亚型的新假说基于激活曲线、神经递质含量和粘膜面积的上呼吸道神经支配它们会使人兴奋。在目标2和目标3中，我们将研究关键刺激剂Up对这些亚t3rpe的激活航空公司调节的反应。具体地说，在目标2中，我们将解决与瞬变的作用相关的假设受体电位Al(TRPAl)在激活上呼吸道伤害性感受器中的作用。TRPA1受体通过以下途径激活广泛的外源物质，包括污染物、食品和烟草烟雾成分。TRPAl 受体也是G蛋白偶联受体激活后下游信号事件的靶标。缓激肽B2受体)。此外，我们提出了新的假设，即TRPA1受体直接被内源性产生的前列腺素J2激活，15-脱氧-2，14-前列腺素J2是 PGD2。在目标3中，我们将解决特定肥大细胞介质影响上呼吸道伤害性感受器的假设。活动通过两种不同的机制：“激活”和“改变兴奋性”。我们还将评估这些机制这些事件是通过它发生的。我们将结合使用解剖学和电生理学技术来致词我们的HJT)Other。