Sensory C Fibers in the Upper Airways

过敏性炎症、外科干预、空气传播引起的上呼吸道感觉神经的激活 污染物和烟草烟雾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。给定反射反应的特定性质可能是由于上部的类型。 被激活的气道传入神经。然而，由于缺乏资料，这方面的进展受到限制 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 存在两种不同化学敏感性（伤害感受器C纤维）感觉神经亚型的新假设 根据激活模式、神经递质含量和粘膜面积支配上呼吸道 它们使神经活动。在目标2和3中，我们将研究这些亚单位的激活，通过关键的兴奋剂上 呼吸道介导的反射。具体来说，在目标2中，我们将讨论与瞬态作用有关的假设。 受体电位A1（TRPA 1）在上气道伤害感受器激活中的作用。TRPA 1受体被激活， 广泛的外源性物质，包括污染物、食品和烟草烟雾成分。TRPAl 受体也是G蛋白偶联受体活化后下游信号传导事件的靶点（例如， 缓激肽B2受体）。此外，我们提出了新的假设，即TRPA 1受体直接参与了细胞的增殖。 由内源性产生的前列腺素类15-脱氧-δ 12，14-前列腺素J2激活， PGD 2.在目的3中，我们将讨论特定肥大细胞介质影响上气道伤害感受器的假设 活性通过两种不同的机制：“激活”和“改变兴奋性”。我们还将评估机制 这些事件的发生。我们将结合解剖学和电生理学技术， 解决我们的问题。

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.