Methacholine-induced airway hyperresponsiveness is dependent on Gαq signaling
Methacholine-induced airway hyperresponsiveness is dependent on Gαq signaling
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DOI：
10.1152/ajplung.00322.2002
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发表时间：
2003-07-01
影响因子：
4.9
通讯作者：
Lee, JJ
中科院分区：
文献类型：
--
作者：
Borchers, MT;Biechele, T;Lee, JJ
健康和疾病中的呼吸道功能以及对支气管痉挛刺激(即刺激物、过敏原和炎症介质)的反应在一定程度上是由平滑肌的胆碱能M受体调节控制的。特别是，气道平滑肌收缩/松弛依赖于异三聚体G蛋白偶联受体信号，这表明这些事件是调节气道功能的反应的基础。含有Galpha(Q)的G蛋白被认为是一条重要的信号通路，而缺乏该亚单位的基因敲除小鼠的可用性使得对其在呼吸道功能中的潜在作用进行了研究。与野生型对照相比，Galpha(Q)缺陷小鼠的呼吸道反应(通过气管张力和体内肺功能测量来评估活动)被减弱。此外，GALPHA(Q)缺陷小鼠的卵蛋白敏化/气雾剂攻击也未能引起过敏原诱导的对乙酰甲胆碱的呼吸道反应性增加。这些发现表明，胆碱能受体介导的反应依赖于Galpha(Q)介导的信号事件，并将Galpha(Q)确定为肺功能障碍预防/干预治疗的潜在靶点。
Airway function in health and disease as well as in response to bronchospastic stimuli (i.e., irritants, allergens, and inflammatory mediators) is controlled, in part, by cholinergic muscarinic receptor regulation of smooth muscle. In particular, the dependence of airway smooth muscle contraction/relaxation on heterotrimeric G protein-coupled receptor signaling suggests that these events underlie the responses regulating airway function. Galpha(q)-containing G proteins are proposed to be a prominent signaling pathway, and the availability of knockout mice deficient of this subunit has allowed for an investigation of its potential role in airway function. Airway responses in Galpha(q)-deficient mice (activities assessed by both tracheal tension and in vivo lung function measurements) were attenuated relative to wild-type controls. Moreover, ovalbumin sensitization/aerosol challenge of Galpha(q)-deficient mice also failed to elicit an allergen-induced increase in airway reactivity to methacholine. These findings indicate that cholinergic receptor-mediated responses are dependent on Galpha(q)-mediated signaling events and identify Galpha(q) as a potential target of preventative/intervening therapies for lung dysfunction.