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The non-neuronal cholinergic system as novel drug target in the airways.

机译：非神经胆碱能系统作为气道中的新型药物靶标。

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摘要

The parasympathetic nervous system is a key regulator of the human organism involved in the pathophysiology of various disorders through cholinergic mechanisms. In the lungs, acetylcholine (ACh) released by vagal nerve endings stimulates muscarinic receptors thereby increasing airway smooth muscle tone. Contraction of airway smooth muscle cells leads to increased respiratory resistance and dyspnea. An additional branch of the cholinergic system is the non-neuronal cholinergic system expressed in nearly all cell types present in the airways. Activation of this system may contribute to an increased cholinergic tone in the lungs, inducing pathophysiological processes like inflammation, remodeling, mucus hypersecretion and chronic cough. Selective muscarinic receptor antagonists specifically inhibit acetylcholine at the receptor inducing bronchodilation in patients with obstructive airway diseases. This paper reviews preclinical pharmacological research activities on anticholinergics including experimental models of asthma and chronic obstructive pulmonary disease, COPD. It discloses various options to follow up the non-neuronal cholinergic system as a novel drug target for the treatment of key aspects of obstructive airway diseases, in particular those of a chronic nature.
机译：副交感神经系统是通过胆碱能机制参与各种疾病的病理生理的人类有机体的关键调节器。在肺部，迷走神经末梢释放的乙酰胆碱（ACh）刺激毒蕈碱受体，从而增加气道平滑肌音调。气道平滑肌细胞收缩导致呼吸阻力增加和呼吸困难。胆碱能系统的另一个分支是在气道中几乎所有细胞类型中表达的非神经元胆碱能系统。该系统的激活可能有助于增加肺中的胆碱能，引起诸如炎症，重塑，粘液分泌过多和慢性咳嗽等病理生理过程。选择性毒蕈碱受体拮抗剂在阻塞性气道疾病患者中特异性抑制乙酰胆碱在该受体上诱导支气管扩张。本文综述了抗胆碱能药物的临床前药理研究活动，包括哮喘和慢性阻塞性肺疾病COPD的实验模型。它公开了跟踪非神经胆碱能系统作为治疗阻塞性气道疾病，特别是慢性疾病的关键方面的新型药物靶标的多种选择。

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