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

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) h...

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Autores principales: Chen, Xi, Feng, Juntao, Hu, Chengping, Qin, Qingwu, Li, Yuanyuan, Qin, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358715/
https://www.ncbi.nlm.nih.gov/pubmed/28035367
http://dx.doi.org/10.3892/ijmm.2016.2836
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author Chen, Xi
Feng, Juntao
Hu, Chengping
Qin, Qingwu
Li, Yuanyuan
Qin, Ling
author_facet Chen, Xi
Feng, Juntao
Hu, Chengping
Qin, Qingwu
Li, Yuanyuan
Qin, Ling
author_sort Chen, Xi
collection PubMed
description 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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spelling pubmed-53587152017-04-06 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 Int J Mol Med Articles 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. D.A. Spandidos 2017-02 2016-12-23 /pmc/articles/PMC5358715/ /pubmed/28035367 http://dx.doi.org/10.3892/ijmm.2016.2836 Text en Copyright: © Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Chen, Xi
Feng, Juntao
Hu, Chengping
Qin, Qingwu
Li, Yuanyuan
Qin, Ling
Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title_full Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title_fullStr Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title_full_unstemmed Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title_short Redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
title_sort redistribution of adrenomedullary nicotinic acetylcholine receptor subunits and the effect on circulating epinephrine levels in a murine model of acute asthma
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358715/
https://www.ncbi.nlm.nih.gov/pubmed/28035367
http://dx.doi.org/10.3892/ijmm.2016.2836
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