Acetylcholine: a novel regulator of airway smooth muscle remodelling?
Increased airway smooth muscle mass is a pathological feature that asthma and chronic obstructive pulmonary disease (COPD) have in common. This increase has gained renewed interest in view of recent developments showing that airway smooth muscle, instead of solely being a contractile partner, is capable of interacting dynamically with its environment, especially under inflammatory conditions. Airway smooth muscle cells are able to proliferate, to migrate, and to secrete chemokines, cytokines, extracellular matrix proteins and growth factors, and most importantly, to adapt to these functions by changing its phenotype from contractile to proliferative/synthetic. Conversely, switching to a (hyper)contractile phenotype may also occur. A vast number of inflammatory stimuli regulate these functions and exert their effects via excitatory G(q) or G(i)-coupled receptors. Since acetylcholine activates muscarinic M(2) and M(3) receptors in the airway smooth muscle cell membrane, which are coupled to G(i) and G(q) proteins, respectively, and since acetylcholine release may be enhanced in airway inflammation, a pathophysiological role of acetylcholine related to the above processes and exceeding contraction could be envisaged. In this review, evidence in favour of this hypothesis, based on recent data that show a role for muscarinic receptors in modulating airway smooth muscle proliferation, contractility and contractile protein expression is discussed. Based on these findings, we postulate that endogenous acetylcholine contributes to airway remodeling in asthma and COPD.
Department of Molecular Pharmacology, University Centre for Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands. r.gosens@farm.rug.nl
Reinoud
R
Gosens
Johan
J
Zaagsma
Mechteld
M
Grootte Bromhaar
Adriaan
A
Nelemans
Herman
H
Meurs
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D002455:Cell Division; D002465:Cell Movement; D003285:Contractile Proteins / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D009130:Muscle, Smooth / Q000378:metabolism / Q000503:physiopathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D012137:Respiratory System / Q000503:physiopathology*; D015398:Signal Transduction
D003285:Contractile Proteins; D000109:Acetylcholine