Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response.
Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response.
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DOI：
10.1155/2013/805627
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发表时间：
2013
影响因子：
--
通讯作者：
Russo M
中科院分区：
文献类型：
--
作者：
Castro JM;Resende RR;Mirotti L;Florsheim E;Albuquerque LL;Lino-dos-Santos-Franco A;Gomes E;de Lima WT;de Franco M;Ribeiro OG;Russo M
由胆碱能激动剂如乙酰甲胆碱（MCh）诱导的气道平滑肌收缩（其通常在哮喘患者中增加）主要由肌肉毒蕈碱M3受体调节，而由迷走神经毒蕈碱M2受体负性调节。在这里，我们评估了基础（内在）和过敏原诱导的（外在）气道反应MCh。我们使用了两种小鼠品系，选择最大限度地（AIRmax）或最小限度地（AIRmin）响应先天性炎症刺激。我们发现，在基础条件下，AIRmin小鼠对MCh的反应比AIRmax更强烈。用特异性M2拮抗剂治疗增加AIRmax小鼠的气道反应，但不增加AIRmin小鼠的气道反应。与AIRmax动物相比，AIRmin动物肺中M2受体的表达显著较低。AIRmax小鼠比AIRmin小鼠产生更强烈的过敏性炎症，并且两种过敏性小鼠系都增加了对MCh的气道反应。然而，没食子胺治疗过敏组不影响对MCh的反应。我们的研究结果证实，低或功能障碍的M2受体活性与气道对MCh的反应性增加有关，并且这种特性在AIRmin小鼠的选择性繁殖过程中遗传，并在变应性肺部炎症期间由AIRmax小鼠获得。
Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh), which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic) and allergen-induced (extrinsic) airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax) or minimally (AIRmin) to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation.
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影响因子：
6.1
作者：
Fryer, AD;Adamko, DJ;Jacoby, DB
通讯作者：
Jacoby, DB
DOI：
10.1165/ajrcmb.23.4.4199
发表时间：
2000-10-01
影响因子：
6.4
作者：
Ewart, SL;Kuperman, D;Wills-Karp, M
通讯作者：
Wills-Karp, M
影响因子：
15.9
作者：
FRYER, AD;JACOBY, DB
通讯作者：
JACOBY, DB
DOI：
10.1164/ajrccm.158.supplement_2.13tac120
发表时间：
1998-11-01
影响因子：
24.7
作者：
Fryer, AD;Jacoby, DB
通讯作者：
Jacoby, DB
影响因子：
6.1
作者：
Bortolatto, J.;Borducchi, E.;Russo, M.
通讯作者：
Russo, M.