Role of intrinsic airway neurons in ozone-induced airway hyperresponsiveness in ferret trachea.
Exposure to ozone (O(3)) enhances airway responsiveness, which is mediated partly by the release of substance P (SP) from airway neurons. In this study, the role of intrinsic airway neurons in O(3)-induced airway responses was examined. Ferrets were exposed to 2 ppm O(3) or air for 1 h. Reactivity of isolated tracheal smooth muscle to cholinergic agonists was significantly increased after O(3) exposure, as were contractions to electrical field stimulation at 10 Hz. Pretreatment with CP-99994, a neurokinin type 1 receptor antagonist, partially abolished the O(3)-induced reactivity to cholinergic agonists and electrical field stimulation. The O(3)-enhanced airway responses were present in tracheal segments cultured for 24 h, a procedure shown to deplete sensory nerves while maintaining viability of intrinsic airway neurons, and all the enhanced smooth muscle responses were also diminished by CP-99994. Immunocytochemistry showed that the percentage of SP-containing neurons in longitudinal trunk and the percentage of neurons innervated by SP-positive nerve fibers in superficial muscular plexus were significantly increased at 1 h after exposure to O(3). These results suggest that enhanced SP levels in airway ganglia contribute to O(3)-induced airway hyperresponsiveness.
Wu
Z X
ZX
Department of Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia 26506, USA.
Maize
D F
DF
Satterfield
B E
BE
Frazer
D G
DG
Fedan
J S
JS
Dey
R D
RD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D046508:Culture Techniques; D004558:Electric Stimulation; D005260:Female; D005289:Ferrets; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010126:Ozone / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000294:innervation* / Q000503:physiopathology; D014133:Tracheal Diseases / Q000139:chemically induced* / Q000503:physiopathology*
D018679:Cholinergic Agonists; D018721:Muscarinic Agonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D016210:Methacholine Chloride; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D010126:Ozone; D000109:Acetylcholine