Muscarinic acetylcholine receptors and airway diseases.
Parasympathetic nerves provide the dominant autonomic innervation of the airways. Release of acetylcholine from parasympathetic nerves activates postjunctional muscarinic receptors present on airway smooth muscle, submucosal glands, and blood vessels to cause bronchoconstriction, mucus secretion, and vasodilatation, respectively. Acetylcholine also feeds back onto prejunctional muscarinic receptors to enhance or inhibit further acetylcholine release. In asthma and chronic obstructive pulmonary disease, bronchoconstriction and mucus secretion is increased and the airways are hyperresponsive to contractile agents. These changes are due to increased parasympathetic nerve activity. The number and function of postjunctional muscarinic receptors in the airways are unchanged in animal models of asthma. Rather, it is the supply of acetylcholine to the postjunctional cells (smooth muscle and submucosal gland) that is increased. The increase in acetylcholine release occurs because prejunctional, inhibitory M(2) muscarinic receptors on the parasympathetic nerves are dysfunctional. M(2) muscarinic receptor dysfunction and subsequent airway hyperreactivity have been demonstrated to occur in animals in response to a variety of triggers, including antigen challenge, virus infection, ozone exposure, and vitamin A deficiency. In humans, there is evidence that loss of M(2) muscarinic receptor function is related to asthma. The mechanisms by which neuronal M(2) muscarinic receptor function is lost and its relevance to human airway disease are discussed in this review.
Coulson
Fiona R
FR
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Fryer
Allison D
AD
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000294:innervation / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D006801:Humans; D009130:Muscle, Smooth / Q000294:innervation / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000503:physiopathology; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000502:physiology*; D012140:Respiratory Tract Diseases / Q000378:metabolism / Q000503:physiopathology*; D012220:Rhinitis / Q000503:physiopathology
D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic