Substance P released from intrinsic airway neurons contributes to ozone-enhanced airway hyperresponsiveness in ferret trachea
Substance P released from intrinsic airway neurons contributes to ozone-enhanced airway hyperresponsiveness in ferret trachea
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DOI：
10.1152/japplphysiol.00109.2003
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发表时间：
2003-08-01
影响因子：
3.3
通讯作者：
Dey, RD
中科院分区：
文献类型：
--
作者：
Wu, ZX;Satterfield, BE;Dey, RD
暴露于臭氧（O-3）诱导气道高反应性，部分通过气道壁神经末梢释放P物质（SP）介导。虽然大量证据表明SP由感觉神经释放，但SP也存在于气道神经节的神经元中。本研究的目的是探讨气管内神经元在O-3增强气管反应性中的作用。为了消除感觉神经支配的影响，在体外暴露于2 ppm的O-3或空气1小时之前，将雪貂气管段在培养条件下保持24小时。通过显示辣椒素不影响气管平滑肌对胆碱能激动剂的反应性或对电场刺激（EFS）的收缩反应来证实感觉神经耗竭。离体气管平滑肌对EFS的收缩反应在体外O-3暴露后显著增加，但对胆碱能激动剂的收缩反应没有改变。预处理与CP-99994，神经激肽1受体的拮抗剂，衰减O-3暴露后的EFS的收缩增加，但在空气暴露组没有效果。O-3暴露后，纵干神经节内SP阳性神经元数、SP对浅肌丛神经元胞体的支配程度和气管平滑肌内SP神经纤维密度均显著增加。结果表明，呼吸道内源性神经元释放的SP通过促进胆碱能神经末梢释放乙酰胆碱而促进O-3增强气管平滑肌反应性。
Exposure to ozone (O-3) induces airway hyperresponsiveness mediated partly through the release of substance P (SP) from nerve terminals in the airway wall. Although substantial evidence suggests that SP is released by sensory nerves, SP is also present in neurons of airway ganglia. The purpose of this study was to investigate the role of intrinsic airway neurons in O-3-enhanced airway responsiveness in ferret trachea. To remove the effects of sensory innervation, segments of ferret trachea were maintained in culture conditions for 24 h before in vitro exposure to 2 parts/million of O-3 or air for 1 h. Sensory nerve depletion was confirmed by showing that capsaicin did not affect tracheal smooth muscle responsiveness to cholinergic agonist or contractility responses to electrical field stimulation (EFS). Contractions of isolated tracheal smooth muscle to EFS were significantly increased after in vitro O-3 exposure, but the constrictor response to cholinergic agonist was not altered. Pretreatment with CP-99994, an antagonist of the neurokinin 1 receptor, attenuated the increased contraction to EFS after O-3 exposure but had no effect in the air exposure group. The number of SP-positive neurons in longitudinal trunk ganglia, the extent of SP innervation to superficial muscular plexus nerve cell bodies, and SP nerve fiber density in tracheal smooth muscle all increased significantly after O-3 exposure. The results show that release of SP from intrinsic airway neurons contributes to O-3-enhanced tracheal smooth muscle responsiveness by facilitating acetylcholine release from cholinergic nerve terminals.