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Muscarinic receptor signaling in the pathophysiology of asthma and COPD.
- Source :
-
Respiratory research [Respir Res] 2006 May 09; Vol. 7, pp. 73. Date of Electronic Publication: 2006 May 09. - Publication Year :
- 2006
-
Abstract
- Anticholinergics are widely used for the treatment of COPD, and to a lesser extent for asthma. Primarily used as bronchodilators, they reverse the action of vagally derived acetylcholine on airway smooth muscle contraction. Recent novel studies suggest that the effects of anticholinergics likely extend far beyond inducing bronchodilation, as the novel anticholinergic drug tiotropium bromide can effectively inhibit accelerated decline of lung function in COPD patients. Vagal tone is increased in airway inflammation associated with asthma and COPD; this results from exaggerated acetylcholine release and enhanced expression of downstream signaling components in airway smooth muscle. Vagally derived acetylcholine also regulates mucus production in the airways. A number of recent research papers also indicate that acetylcholine, acting through muscarinic receptors, may in part regulate pathological changes associated with airway remodeling. Muscarinic receptor signalling regulates airway smooth muscle thickening and differentiation, both in vitro and in vivo. Furthermore, acetylcholine and its synthesizing enzyme, choline acetyl transferase (ChAT), are ubiquitously expressed throughout the airways. Most notably epithelial cells and inflammatory cells generate acetylcholine, and express functional muscarinic receptors. Interestingly, recent work indicates the expression and function of muscarinic receptors on neutrophils is increased in COPD. Considering the potential broad role for endogenous acetylcholine in airway biology, this review summarizes established and novel aspects of muscarinic receptor signaling in relation to the pathophysiology and treatment of asthma and COPD.
- Subjects :
- Acetylcholine metabolism
Animals
Asthma drug therapy
Asthma pathology
Bronchodilator Agents pharmacology
Bronchodilator Agents therapeutic use
Cell Differentiation
Cell Proliferation
Fibroblasts drug effects
Fibroblasts metabolism
Fibroblasts pathology
Humans
Lung drug effects
Lung innervation
Lung metabolism
Lymphocytes metabolism
Lymphocytes pathology
Mucus metabolism
Muscarinic Antagonists pharmacology
Muscarinic Antagonists therapeutic use
Muscle, Smooth drug effects
Muscle, Smooth innervation
Muscle, Smooth metabolism
Neutrophils metabolism
Neutrophils pathology
Pulmonary Disease, Chronic Obstructive drug therapy
Pulmonary Disease, Chronic Obstructive metabolism
Pulmonary Disease, Chronic Obstructive pathology
Receptors, Muscarinic drug effects
Scopolamine Derivatives pharmacology
Scopolamine Derivatives therapeutic use
Tiotropium Bromide
Asthma physiopathology
Pulmonary Disease, Chronic Obstructive physiopathology
Receptors, Muscarinic metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1465-993X
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Respiratory research
- Publication Type :
- Academic Journal
- Accession number :
- 16684353
- Full Text :
- https://doi.org/10.1186/1465-9921-7-73