Substance P released from intrinsic airway neurons contributes to ozone-enhanced airway hyperresponsiveness in ferret trachea.
Exposure to ozone (O3) 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 O3-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 O3 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 O3 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 O3 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 O3 exposure. The results show that release of SP from intrinsic airway neurons contributes to O3-enhanced tracheal smooth muscle responsiveness by facilitating acetylcholine release from cholinergic nerve terminals.
Department of Neurobiology and Anatomy, West Virginia University, Morgantown, WV 26506, USA.
Zhong-Xin
ZX
Wu
Brian E
BE
Satterfield
Richard D
RD
Dey
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005289:Ferrets; D005724:Ganglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000378:metabolism*; D010126:Ozone / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D010126:Ozone; D002211:Capsaicin