Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma

Chen,Xi; Feng,Juntao; Hu,Chengping; Qin,Qingwu; Li,Yuanyuan; Qin,Ling

doi:10.3892/ijmm.2016.2836

Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma

Authors:
- Xi Chen
- Juntao Feng
- Chengping Hu
- Qingwu Qin
- Yuanyuan Li
- Ling Qin
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Affiliations: Department of Respiratory Medicine, Xiangya Hospital, Central South University (Key Site of the National Clinical Research Center for Respiratory Disease), Changsha, Hunan 410008, P.R. China
Published online on: December 23, 2016 https://doi.org/10.3892/ijmm.2016.2836
Pages: 337-346
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The lack of circulating epinephrine (EPI) in the pathogenesis of asthma has long been attributed to the lack of adrenergic nerves in human airways. However, in this study we considered that EPI levels are regulated by EPI release in addition to synthesis. Nicotinic acetylcholine receptors (nAChRs) have been shown to control EPI release, and we hypothesized that redistribution of nAChR subunits modulates EPI release and circulating EPI levels. Using a mouse model of asthma, circulating EPI levels were measured by enzyme-linked immunosorbent assays. Changes in the expression of nAChR subunits in the adrenal medulla were observed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Expression of phenylethanolamine N-methyltransferase, tyrosine hydroxylase and galanin was detected by RT-qPCR. Lung pathology, airway resistance (RL) and EPI levels were also assessed after treatment with an α7 nAChR agonist or antagonist. α7 nAChR mRNA expression in the adrenal medulla was increased by more than 2-fold (P<0.05), and circulating EPI levels increased rapidly after treatment with the α7 nAChR agonist. These results indicated that increased EPI release, which was caused by the overexpression of α7 nAChR, was responsible for elevated circulating EPI levels. After treatment with an agonist of α7 nAChR, RL was significantly decreased. Serum corticosterone levels in individual mice were measured to rule out glucocorticoid as the main mediator of changes in EPI levels. On the whole, redistribution of nAChR subunits, primarily α7 nAChR, occurs in the adrenal medulla in asthmatic mice. Increased α7 nAChR expression can rapidly increase serum EPI levels and decrease airway responsiveness.

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