Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

Muscarinic receptors are expressed by most cell types and mediate cellular signaling of their natural ligand acetylcholine. Thereby, they control numerous central and peripheral physiological organ responses to neuronal activity. In the human lung, muscarinic receptors are predominantly expressed by...

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Main Authors: George Karakiulakis, Michael Roth
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/409580
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author George Karakiulakis
Michael Roth
author_facet George Karakiulakis
Michael Roth
author_sort George Karakiulakis
collection DOAJ
description Muscarinic receptors are expressed by most cell types and mediate cellular signaling of their natural ligand acetylcholine. Thereby, they control numerous central and peripheral physiological organ responses to neuronal activity. In the human lung, muscarinic receptors are predominantly expressed by smooth muscle cells, epithelial cells, and fibroblasts. Antimuscarinic agents are used for the treatment of chronic obstructive pulmonary disease and to a lesser extent for asthma. They are primarily used as bronchodilators, but it is now accepted that they are also associated with anti-inflammatory, antiproliferative, and antiremodeling effects. Remodeling of the small airways is a major pathology in COPD and impairs lung function through changes of the extracellular matrix. Glycosaminoglycans, particularly hyaluronic acid, and matrix metalloproteases are among extracellular matrix molecules that have been associated with tissue inflammation and remodeling in lung diseases, including chronic obstructive pulmonary disease and asthma. Since muscarinic receptors have been shown to influence the homeostasis of glycosaminoglycans and matrix metalloproteases, these molecules may be proved valuable endpoint targets in clinical studies for the pharmacological exploitation of the anti-inflammatory and antiremodeling effects of muscarinic inhibitors in the treatment of chronic obstructive pulmonary disease and asthma.
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spelling doaj-art-95a242757e1a4d9196e7fa1edce5c9992025-08-20T03:20:33ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/409580409580Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling EffectsGeorge Karakiulakis0Michael Roth1Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreecePulmonary Cell Research-Pneumology, University Hospital Basel, 4031 Basel, SwitzerlandMuscarinic receptors are expressed by most cell types and mediate cellular signaling of their natural ligand acetylcholine. Thereby, they control numerous central and peripheral physiological organ responses to neuronal activity. In the human lung, muscarinic receptors are predominantly expressed by smooth muscle cells, epithelial cells, and fibroblasts. Antimuscarinic agents are used for the treatment of chronic obstructive pulmonary disease and to a lesser extent for asthma. They are primarily used as bronchodilators, but it is now accepted that they are also associated with anti-inflammatory, antiproliferative, and antiremodeling effects. Remodeling of the small airways is a major pathology in COPD and impairs lung function through changes of the extracellular matrix. Glycosaminoglycans, particularly hyaluronic acid, and matrix metalloproteases are among extracellular matrix molecules that have been associated with tissue inflammation and remodeling in lung diseases, including chronic obstructive pulmonary disease and asthma. Since muscarinic receptors have been shown to influence the homeostasis of glycosaminoglycans and matrix metalloproteases, these molecules may be proved valuable endpoint targets in clinical studies for the pharmacological exploitation of the anti-inflammatory and antiremodeling effects of muscarinic inhibitors in the treatment of chronic obstructive pulmonary disease and asthma.http://dx.doi.org/10.1155/2012/409580
spellingShingle George Karakiulakis
Michael Roth
Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
Mediators of Inflammation
title Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
title_full Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
title_fullStr Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
title_full_unstemmed Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
title_short Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects
title_sort muscarinic receptors and their antagonists in copd anti inflammatory and antiremodeling effects
url http://dx.doi.org/10.1155/2012/409580
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