Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux
Muscarinic receptors involved in airway vascular leakage induced by experimental gastro-oesophageal reflux
复制标题
毒蕈碱受体参与实验性胃食管反流诱导的气道血管渗漏。
DOI：
10.1016/j.lfs.2008.02.008
复制
发表时间：
2008-04-23
期刊：
影响因子：
6.1
通讯作者：
Devillier, Philippe
中科院分区：
文献类型：
--
作者：
Cui, Yong-Yao;Zhu, Liang;Devillier, Philippe
胃食管酸反流可引起哮喘患者的气道反应，如咳嗽、支气管收缩和炎症。对人类或动物的研究表明，这些反应涉及胆碱能神经。本研究旨在探讨迷走神经传出成分在豚鼠食管滴注盐酸（HCl）引起的气道微血管渗漏中的作用及相关的M受体亚型。双侧迷走神经切断术或烟碱受体拮抗剂六甲双铵可消除食管内盐酸灌注引起的气道微血管渗漏。盐酸诱导的渗漏抑制预处理阿托品，非特异性毒蕈碱受体拮抗剂，也预处理哌仑西平，毒蕈碱M，受体拮抗剂，或4-DAMP，毒蕈碱M-3受体拮抗剂。哌仑西平比阿托品和4-DAMP更有效。这些拮抗剂也研究了对气道微血管渗漏或静脉注射乙酰胆碱（ACh）引起的支气管收缩。阿托品，哌仑西平和4-DAMP抑制乙酰胆碱诱导的气道微血管渗漏具有相似的效力。与此形成鲜明对比的是，4-DAMP和阿托品是比哌仑西平更有效的ACh诱导的支气管收缩抑制剂。毒蕈碱M-2受体拮抗剂Methoctramine在所有实验条件下均无效。这些结果表明，HCI食管内滴注引起的气道微血管渗漏涉及ACh从迷走神经末梢的释放和M，M-3受体发挥了主要作用，胆碱能介导的微血管渗漏，而M-3受体主要参与乙酰胆碱诱导的支气管收缩。(c)2008年爱思唯尔公司All rights reserved.
Gastro-oesophageal acid reflux may cause airway responses such as cough, bronchoconstriction and inflammation in asthmatic patients. Studies in humans or in animals have suggested that these responses involve cholinergic nerves. The purpose of this study was to investigate the role of the efferent vagal component on airway microvascular leakage induced by instillation of hydrochloric acid (HCI) into the oesophagus of guinea-pigs and the subtype of muscarinic receptors involved. Airway microvascular leakage induced by intra-oesophageal HCI instillation was abolished by bilateral vagotomy or by the nicotinic receptor antagonist, hexamethonium. HCl-induced leakage was inhibited by pretreatment with atropine, a non-specific muscarinic receptor antagonist, and also by pretreatment with either pirenzepine, a muscarinic M, receptor antagonist, or 4-DAMP, a muscarinic M-3 receptor antagonist. Pirenzepine was more potent than atropine and 4-DAMP. These antagonists were also studied on airway microvascular leakage or bronchoconstriction induced by intravenous administration of acetylcholine (ACh). Atropine, pirenzepine and 4-DAMP inhibited ACh-induced airway microvascular leakage with similar potencies. In sharp contrast, 4-DAMP and atropine were more potent inhibitors of ACh-induced bronchoconstriction than pirenzepine. Methoctramine, a muscarinic M-2 receptor antagonist, was ineffective in all experimental conditions. These results suggest that airway microvascular leakage caused by HCI intra-oesophageal instillation involves ACh release from vagus nerve terminals and that M, and M-3 receptors play a major role in cholinergic-mediated microvascular leakage, whereas M-3 receptors are mainly involved in ACh-induced bronchoconstriction. (c) 2008 Elsevier Inc. All rights reserved.