Pulmonary neuronal M2 muscarinic receptor function in asthma and animal models of hyperreactivity

• Published in: Thorax Vol. 53; no. 7; pp. 613 - 618
• Main Authors: COSTELLO, R. W, JACOBY, D. B, FRYER, A. D
• Format: Journal Article
• Language: English
• Published: London BMJ 01.07.1998; BMJ Group
• Subjects: Acetylcholine - metabolism; Animals; Asthma - metabolism; Biological and medical sciences; Bronchial Hyperreactivity - metabolism; Chronic obstructive pulmonary disease, asthma; Disease Models, Animal; Eosinophils - metabolism; Guinea Pigs; Humans; Inflammation Mediators - metabolism; Lung - metabolism; Medical sciences; Occasional Review; Parasympathetic Nervous System - physiology; Pneumology; Receptor, Muscarinic M2; Receptors, Muscarinic - physiology; Human; Pathophysiology; Respiratory disease; Autonomic nervous system; Animal; Lung; M2 Muscarinic receptor; Obstructive pulmonary disease; Review; Asthma; Cholinergic pathway
• ISSN: 0040-6376; 1468-3296
• DOI: 10.1136/thx.53.7.613

In the lungs neuronal M2 muscarinic receptors limit acetylcholine release from postganglionic cholinergic nerves. These inhibitory M2 receptors are dysfunctional in antigen challenged guinea pigs and in humans with asthma which leads to an increase in vagally mediated hyperreactivity. In vitro, eosinophil products act as allosteric antagonists at neuronal M2 muscarinic receptors. In vivo, displacing or neutralising MBP preserves neuronal M2 muscarinic receptor function and prevents hyperreactivity. Thus, there is good evidence from animal studies that after antigen challenge pulmonary M2 muscarinic receptors become dysfunctional because MBP inhibits their function. Loss of function of pulmonary neuronal M2 muscarinic receptors has also been reported in patients with asthma, although the clinical significance of this dysfunction and the mechanisms underlying it are not yet established.