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 language | English (US) |
|---|---|
| Pages (from-to) | 59-69 |
| Number of pages | 11 |
| Journal | Pharmacology and Therapeutics |
| Volume | 98 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 1 2003 |
| Externally published | Yes |
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Keywords
- Airway hyperreactivity
- Eosinophils
- Parasympathetic nerves
- Postjunctional receptors
- Prejunctional receptors
- Viruses
ASJC Scopus subject areas
- Pharmacology
Cite this
Muscarinic acetylcholine receptors and airway diseases. / Coulson, Fiona R.; Fryer, Allison.
In: Pharmacology and Therapeutics, Vol. 98, No. 1, 01.04.2003, p. 59-69.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Muscarinic acetylcholine receptors and airway diseases
AU - Coulson, Fiona R.
AU - Fryer, Allison
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
KW - Airway hyperreactivity
KW - Eosinophils
KW - Parasympathetic nerves
KW - Postjunctional receptors
KW - Prejunctional receptors
KW - Viruses
UR - http://www.scopus.com/inward/record.url?scp=0037377578&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037377578&partnerID=8YFLogxK
U2 - 10.1016/S0163-7258(03)00004-4
DO - 10.1016/S0163-7258(03)00004-4
M3 - Article
C2 - 12667888
AN - SCOPUS:0037377578
VL - 98
SP - 59
EP - 69
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
SN - 0163-7258
IS - 1
ER -