title: A new perspective on muscarinic receptor antagonism in obstructive airways diseases.
abstract: Acetylcholine has traditionally only been regarded as a neurotransmitter of the parasympathetic nervous system, causing bronchoconstriction and mucus secretion in asthma and COPD by muscarinic receptor activation on airway smooth muscle and mucus-producing cells. Recent studies in experimental models indicate that muscarinic receptor stimulation in the airways also induces pro-inflammatory, pro-proliferative and pro-fibrotic effects, which may involve activation of airway structural and inflammatory cells by neuronal as well as non-neuronal acetylcholine. In addition, mechanical changes caused by muscarinic agonist-induced bronchoconstriction may be involved in airway remodeling. Crosstalk between muscarinic receptors and β2-adrenoceptors on airway smooth muscle causes a reduced bronchodilator response to β2-agonists, and a similar mechanism could possibly apply to the poor inhibition of inflammatory and remodeling processes by these drugs. Collectively, these findings provide novel perspectives for muscarinic receptor antagonists in asthma and COPD, since these drugs may not only acutely affect cholinergic airways obstruction, but also have important beneficial effects on β2-agonist responsiveness, airway inflammation and remodeling. The clinical relevance of these findings is presently under investigation and starting to emerge.
authors: Department of Molecular Pharmacology, Groningen Research Institute for Pharmacy, University of Groningen, The Netherlands. h.meurs@rug.nl
authors: Herman
authors: H
authors: Meurs
authors: Tjitske A
authors: TA
authors: Oenema
authors: Loes E M
authors: LE
authors: Kistemaker
authors: Reinoud
authors: R
authors: Gosens
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018727:Muscarinic Antagonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic