title: Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling.
abstract: Acetylcholine is the primary parasympathetic neurotransmitter in the airways, where it not only induces bronchoconstriction and mucus secretion, but also regulates airway inflammation and remodeling. In this review, we propose that these effects are all primarily mediated via the muscarinic M3 receptor. Acetylcholine promotes inflammation and remodeling via direct effects on airway cells, and via mechanical stress applied to the airways sequential to bronchoconstriction. The effects on inflammation and remodeling are regulated by both neuronal and non-neuronal acetylcholine. Taken together, we believe that the combined effects of anticholinergic therapy on M3-mediated bronchoconstriction, mucus secretion, inflammation, and remodeling may account for the positive outcome of treatment with these drugs for patients with chronic pulmonary obstructive disease (COPD) or asthma.
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: l.e.m.kistemaker@rug.nl.
authors.forename: Loes E M
authors.initials: LE
authors.lastname: Kistemaker
authors.affiliation: Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands; GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: r.gosens@rug.nl.
authors.forename: Reinoud
authors.initials: R
authors.lastname: Gosens
mesh_terms: D000109:Acetylcholine / Q000378:metabolism* / Q000502:physiology; D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016084:Bronchoconstriction; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D011976:Receptors, Muscarinic / Q000378:metabolism* / Q000502:physiology
chemical_list: D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D011976:Receptors, Muscarinic; D000109:Acetylcholine
keywords: M(3) receptor; anticholinergics; mechanical strain; muscarinic receptor subtypes; non-neuronal acetylcholine