Abstract

Release of acetylcholine from parasympathetic nerves in the airways activates postjunctional muscarinic receptors present on smooth muscle, submucosal glands and blood vessels. This triggers bronchoconstriction, muscle hypertrophy, mucus secretion, and vasodilatation, respectively. The release of acetylcholine from parasympathetic nerves in lungs is induced by a variety of stimuli and downregulated by the inhibitory activity of neuronal M2 muscarinic receptors via a feedback mechanism. Increased parasympathetic nerve activity occurs in a variety of airway diseases in childhood, including viral-induced wheeze and asthma. Common to these conditions are reversible airway obstruction, mucus hypersecretion, vasodilation and enhanced vascular permeability. In animal models of airway hyperreactivity similar findings of increased acetylcholine release resulting in enhanced supply of this neurotransmitter to the postjunctional smooth muscles, submucosal glands and airway vessels, were demonstrated. While the number and function of postjunctional muscarinic receptors in the airways are unchanged in such airway disorders, inhibitory activity on the parasympathetic nerves appears to be impaired. Specifically, M2 muscarinic receptor dysfunction has been demonstrated in models of bronchial hyperreactivity induced by a variety of triggers, including viruses, atmospheric pollutants and allergens. The mechanisms leading to impairment of neuronal M2 muscarinic receptor function and their putative relevance to the pathogenesis and the treatment of airway disease in childhood are described. Finally, the available data on the activity of ipratropium bromide, a short-acting anticholinergic drug, in the most common pediatric airway disease are reported and the possible therapeutic efficacy of tiotropium bromide, a more recently introduced long-acting, selective anticholinergic compound, is discussed.

Links

Publisher Full Text

Publisher Full Text

Authors

Quizon A, Colin AA, Pelosi U, Rossi GA

Institution

Division of Pediatric Pulmonology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Source

Current pharmaceutical design 18:21 2012 pg 3061-85

MeSH

Airway Obstruction
Child
Child, Preschool
Cholinergic Antagonists
Humans
Infant
Lung
Parasympathetic Nervous System
Receptor Cross-Talk
Receptors, Muscarinic
Receptors, Nicotinic

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

22564300