title: The non-neuronal cholinergic system as novel drug target in the airways.
abstract: 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.
authors.affiliation: Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. michael.pieper@boehringer-ingelheim.com
authors.forename: Michael Paul
authors.initials: MP
authors.lastname: Pieper
mesh_terms: D000109:Acetylcholine / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000294:innervation / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000276:immunology / Q000378:metabolism*
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine