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学科主题: 临床医学
题名:
Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus
作者: Liu, Zhenyu1,2; Hu, Youtian2; Yu, Xiaoyun2; Xi, Jiefeng3; Fan, Xiaoming4; Tse, Chung-Ming2; Myers, Allen C.2; Pasricha, Pankaj J.2; Li, Xingde3; Yu, Shaoyong2
关键词: eosinophilic esophagitis ; nodose ; jugular ; dysphagia ; heartburn
刊名: AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
发表日期: 2015-03-15
DOI: 10.1152/ajpgi.00374.2014
卷: 308, 期:6, 页:G482-G488
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Gastroenterology & Hepatology ; Physiology
研究领域[WOS]: Gastroenterology & Hepatology ; Physiology
关键词[WOS]: EXPERIMENTAL EOSINOPHILIC ESOPHAGITIS ; MAST-CELL ACTIVATION ; MECHANICAL HYPERSENSITIVITY ; INFLAMMATION ; DERMATITIS ; BRADYKININ ; ANKTM1 ; PAIN
英文摘要:

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′, 3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE.

语种: 英语
所属项目编号: DK087991
项目资助者: NIH
WOS记录号: WOS:000351063500003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/49872
Appears in Collections:北京大学深圳医院_期刊论文

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作者单位: 1.Fudan Univ, Div Gastroenterol & Hepatol, Jinshan Hosp, Shanghai 200433, Peoples R China
2.Peking Univ, Shenzhen Hosp, Div Gastroenterol, Shenzhen, Peoples R China
3.Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
4.Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

Recommended Citation:
Liu, Zhenyu,Hu, Youtian,Yu, Xiaoyun,et al. Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus[J]. AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY,2015,308(6):G482-G488.
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