神经生长因子
原肌球蛋白受体激酶A
TRPV1型
医学
咳嗽反射
敌手
脑干
内分泌学
药理学
气道
内科学
受体
麻醉
瞬时受体电位通道
作者
Ahmed Z. El‐Hashim,Sahar M. Jaffal,Fatma T. Al-Rashidi,Yunus A. Luqmani,Saghir Akhtar
标识
DOI:10.1016/j.phrs.2013.05.003
摘要
The mechanisms involved in enhanced cough induced by central and inhaled NGF in guinea pigs were investigated. Cough and airway function were assessed by plethysmography following inhaled or intracerebroventricular (i.c.v.) NGF treatment. Expression of TrkA and/or TRPV1 was determined in bronchi and/or brainstem by real-time PCR and immunoblotting. I.c.v. and inhaled NGF enhanced citric acid induced-cough and airway obstruction. Pretreatment (i.c.v.) with antagonists of TrkA (K252a) or TRPV1 (IRTX) significantly reduced both the NGF (i.c.v.) enhanced cough and airway obstruction whereas the NK1 antagonist (FK888) inhibited only cough. The H1 antagonist (cetirizine) did not affect either. Inhaled NGF increased phosphorylation of TrkA receptors in the bronchi but not the brainstem at 0.5 h post-treatment. TrkA mRNA was elevated at 0.5 h in the bronchi and at 24 h in the brainstem while TRPV1 mRNA was elevated from 0.5 h to 24 h in brainstem and at 24 h in the bronchi. Pretreatment (i.c.v.) with IRTX, but not K252a, significantly inhibited the inhaled NGF-enhanced cough. Central NGF administration enhances cough and airway obstruction by mechanisms dependent on central activation of TrkA, TRPV1 and NK1 receptors while inhaled NGF enhances cough via a mechanism dependent on central TRPV1 and not TrkA receptors. These data show that NGF, in addition to its effects on the airways, has an important central mechanism of action in the enhancement of cough. Therefore, therapeutic strategies targeting NGF signaling in both the airways and CNS may be more effective in the management of cough.
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