Kageyama N, Ichinose M, Igarashi A, Miura M, Yamauchi H, Sasaki Y, Ishikawa J, Tomaki M, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Eur Respir J. 1996 Jul;9(7):1439-44. doi: 10.1183/09031936.96.09071439.
The effect of repeated allergen inhalation challenge on the airway excitatory nonadrenergic noncholinergic (e-NANC) nerve-mediated bronchoconstrictor response was studied in ovalbumin (OA) sensitized guinea-pigs. Three weeks after sensitization, OA inhalation, 0.03% for 3 min (challenged group), or saline inhalation (control group) was repeated every day for 4 weeks. The e-NANC nerve function was examined in vitro by means of isometric tension measurement of main bronchi. After pretreatment with atropine (10(-6) M) and propranolol (10(-6) M), we performed electrical field stimulation (EFS) or exogenous neurokinin A (NKA) administration. In the challenged group, EFS-induced main bronchial contraction was significantly greater than that of the control group (p < 0.05 or p < 0.01), but exogenous NKA-mediated responses were almost the same in both groups. The e-NANC-induced main bronchial contractions after EFS were enhanced by pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, to the same degree in the control and challenged groups, indicating that the peptide degradation mechanisms were not impaired even in the challenged group. Substance P immunoreactivities in the lung of the challenged group were significantly higher than those of the control group. These results suggest that chronic airway inflammation after repeated allergen challenge increases excitatory nonadrenergic noncholinergic nerve function, possibly by enhancing sensory neuropeptide production and/or release.
在卵清蛋白（OA）致敏的豚鼠中，研究了反复吸入变应原激发对气道兴奋性非肾上腺素能非胆碱能（e-NANC）神经介导的支气管收缩反应的影响。致敏3周后，每天重复吸入0.03%的OA 3分钟（激发组）或吸入生理盐水（对照组），共4周。通过主支气管等长张力测量在体外检测e-NANC神经功能。在用阿托品（10^(-6) M）和普萘洛尔（10^(-6) M）预处理后，进行电场刺激（EFS）或给予外源性神经激肽A（NKA）。在激发组中，EFS诱导的主支气管收缩明显大于对照组（p < 0.05或p < 0.01），但两组中外源性NKA介导的反应几乎相同。在对照组和激发组中，用中性内肽酶抑制剂磷酰胺素预处理后，EFS后e-NANC诱导的主支气管收缩增强程度相同，表明即使在激发组中肽降解机制也未受损。激发组肺中P物质免疫反应性明显高于对照组。这些结果表明，反复变应原激发后的慢性气道炎症可能通过增强感觉神经肽的产生和/或释放来增加兴奋性非肾上腺素能非胆碱能神经功能。
