Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients.
Enhanced nicotinic receptor mediated relaxations in gastroesophageal muscle fibers from Barrett's esophagus patients.
复制标题
增强的烟碱受体介导巴雷特食管患者胃食管肌纤维的松弛。
DOI：
10.1111/nmo.12294
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
RuggieriSr,MR
中科院分区：
文献类型：
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作者：
Miller,LS;Vegesna,AK;Braverman,AS;Barbe,MF;RuggieriSr,MR
背景烟碱受体介导的胃食管抗反流屏障松弛的增加可能与反流的病理生理学有关。本研究旨在确定我们之前在胃食管反流病患者体内发现的缺陷是否是由于胃吊带、胃扣或食管下环 (LEC) 肌纤维的异常所致。方法从 16 名正常供体和 15 名经组织学证明患有巴雷特食管的供体中获取整个胃和食管的肌肉条。在诱导氨甲酰甲胆碱最大收缩后，测定胃吊带、胃扣或 LEC 纤维对增加卡巴胆碱和尼古丁浓度的收缩和松弛反应。使用亚型选择性免疫沉淀法测量毒蕈碱受体密度。关键结果Barrett 食管胃吊带和 LEC 纤维减少了卡巴胆碱诱导的收缩。 Barrett 食管吊带纤维的 M2 毒蕈碱受体减少，LEC 纤维的 M3 受体减少。在巴雷特食管标本中，对于高卡巴胆碱浓度和氨甲酰胆碱预收缩后的尼古丁，所有三种纤维类型的松弛程度都更大。 Barrett 食管吊带和 LEC 纤维对氨甲酰胆碱的最大反应更大。结论与推论 Barrett 标本中对氨甲酰胆碱的收缩反应增加表明缺陷可能不是由于平滑肌本身造成的。增强的烟碱受体介导的反应可能与食管下端括约肌短暂松弛和吞咽抑制期间胃食管交界处高压区内肌肉的更大松弛有关，并且可能与胃食管反流病的病理生理学有关。
BackgroundIncreased nicotinic receptor mediated relaxation in the gastroesophageal antireflux barrier may be involved in the pathophysiology of reflux. This study is designed to determine whether the defects we previously identified in gastroesophageal reflux disease patients in‐ vivo are due to abnormalities of the gastric sling, gastric clasp, or lower esophageal circular (LEC) muscle fibers.MethodsMuscle strips from whole stomachs and esophagi were obtained from 16 normal donors and 15 donors with histologically proven Barrett's esophagus. Contractile and relaxant responses of gastric sling, gastric clasp, or LEC fibers were determined to increasing concentrations of carbachol and to nicotine after inducing maximal contraction to bethanechol. Muscarinic receptor density was measured using subtype selective immunoprecipitation.Key ResultsBarrett's esophagus gastric sling and LEC fibers have decreased carbachol‐induced contractions. Barrett's esophagus sling fibers have decreased M2‐muscarinic receptors and LEC fibers have decreased M3receptors. Relaxations of all three fiber types are greater in Barrett's esophagus specimens to both high carbachol concentrations and to nicotine following bethanechol precontraction. The maximal response to bethanechol is greater in Barrett esophagus sling and LEC fibers.Conclusions & InferencesThe increased contractile response to bethanechol in Barrett's specimens indicates that the defect is likely not due to the smooth muscle itself. The enhanced nicotinic receptor mediated response may be involved in greater relaxation of the muscles within the high‐pressure zone of the gastroesophageal junction during transient lower esophageal sphincter relaxations and during deglutitive inhibition and may be involved in the pathophysiology of gastroesophageal reflux disease.