Muscarinic receptors and control of airway smooth muscle
Muscarinic receptors and control of airway smooth muscle
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DOI：
10.1164/ajrccm.158.supplement_2.13tac120
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发表时间：
1998-11-01
影响因子：
24.7
通讯作者：
Jacoby, DB
中科院分区：
文献类型：
--
作者：
Fryer, AD;Jacoby, DB
气道平滑肌收缩是由气道平滑肌上的M-3毒蕈碱受体介导的。然而，没有证据表明高反应性是由这些M-3毒蕈碱受体的功能改变引起的。相反，在多动症和哮喘动物模型中，神经递质乙酰胆碱的释放明显增加。乙酰胆碱的释放由抑制性M-2毒蕈碱受体控制，在高反应性动物模型中，似乎正是这些M-2受体功能失调。过敏原诱导的M-2受体功能障碍完全依赖于嗜酸性粒细胞流入气道。活化的嗜酸性粒细胞释放与M-2受体结合并阻止乙酰胆碱结合的主要碱性蛋白。因此，乙酰胆碱释放的正常负反馈控制丧失，乙酰胆碱释放增加。总之，抑制M-2毒蕈碱受体在气道副交感神经上的功能丧失导致抗原刺激后迷走神经介导的支气管收缩和高反应性。
Contraction of airway smooth muscle is mediated by M-3 muscarinic receptors on the airway smooth muscle. However, there is no evidence suggesting that hyperresponsiveness results from any alterations in function of these M-3 muscarinic receptors. In contrast, there is clearly increased release of the neurotransmitter acetylcholine in animal models of hyperactivity and in asthma. Release of acetylcholine is controlled by inhibitory M-2 muscarinic receptors, and it appears that it is these M-2 receptors that are dysfunctional in animal models of hyperresponsiveness. Allergen-induced M-2 receptor dysfunction is absolutely dependent upon an influx of eosinophils into the airways. Activated eosinophils release major basic protein, which binds to M-2 receptors and prevents binding of acetylcholine. Thus, the normal negative feedback control of acetylcholine release is lost, and acetylcholine release is increased. In conclusion, loss of function of inhibitory M-2 muscarinic receptors on the airway parasympathetic nerves causes vagally mediated bronchoconstriction and hyperresponsiveness following antigen challenge.