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.

通过过敏性炎症，外科干预，空气传播的上呼吸道激活感觉神经污染物和烟草烟雾启动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。给定反射响应的特定性质可能是由于上张的类型激活的气道传入神经。但是，该领域的进展受到缺乏信息的限制关于上呼吸道的感觉神经亚型及其激活机制。在AIM 1中，我们将解决新的假设是有两个不同的化学敏感（伤害感受器C纤维）感觉神经亚型基于激活曲线，神经递质含量和粘膜面积来支配上部气道他们支配了。在目标2和3中，我们将通过上部的关键兴奋剂研究这些微分3RP的激活气道介导的反射。具体而言，在AIM 2中，我们将解决与瞬态作用有关的假设上呼吸道伤害感受器激活中受体电位AL（TRPAL）。 TRPAL受体被激活多种外源物质，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传导事件的靶标（例如 Bradykinin B2受体）。另外，我们提出了新的假设，即TRPAL受体直接由内生产的前列腺素15-脱氧于2,14-prostaglandin J2激活，这是一种代谢产物 PGD2。在AIM 3中，我们将解决特定肥大细胞介质影响上气道伤害感受器的假设通过2种不同的机制进行活动：“激活”和“改变的兴奋性”。我们还将评估机制发生这些事件的情况。我们将使用解剖学和电生理技术的组合解决我们的hjt）。