Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
Life Sci. 2012 Nov 27;91(21-22):1113-8. doi: 10.1016/j.lfs.2012.08.030. Epub 2012 Sep 6.
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.
副交感神经系统是人类机体的一个关键调节系统，通过胆碱能机制参与各种疾病的病理生理学。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张力。气道平滑肌细胞的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非神经元胆碱能系统，存在于气道中几乎所有的细胞类型中。该系统的激活可能导致肺部胆碱能张力增加，引发炎症、重塑、黏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特异性地在受体部位抑制乙酰胆碱，从而在阻塞性气道疾病患者中诱导支气管扩张。本文综述了抗胆碱能药物的临床前药理学研究活动，包括哮喘和慢性阻塞性肺疾病（COPD）的实验模型。它揭示了各种选择来跟踪非神经元胆碱能系统作为治疗阻塞性气道疾病关键方面的新型药物靶点，特别是那些具有慢性性质的疾病。
