Muscarinic acetylcholine receptors and airway diseases

Fiona R. Coulson, Allison D. Fryer

Research output: Contribution to journalReview article

150 Scopus citations

Abstract

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 M2 muscarinic receptors on the parasympathetic nerves are dysfunctional. M2 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 M2 muscarinic receptor function is related to asthma. The mechanisms by which neuronal M2 muscarinic receptor function is lost and its relevance to human airway disease are discussed in this review.

Original languageEnglish (US)
Pages (from-to)59-69
Number of pages11
JournalPharmacology and Therapeutics
Volume98
Issue number1
DOIs
StatePublished - Apr 1 2003

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Keywords

  • Airway hyperreactivity
  • Eosinophils
  • Parasympathetic nerves
  • Postjunctional receptors
  • Prejunctional receptors
  • Viruses

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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