title: Pulmonary neuronal M2 muscarinic receptor function in asthma and animal models of hyperreactivity.
abstract: 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.
authors.affiliation: Department of Medicine, University of Liverpool, UK.
authors.forename: R W
authors.initials: RW
authors.lastname: Costello
authors.forename: D B
authors.initials: DB
authors.lastname: Jacoby
authors.forename: A D
authors.initials: AD
authors.lastname: Fryer
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000378:metabolism*; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000502:physiology; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D000109:Acetylcholine