Abstract
M2 muscarinic receptors limit acetylcholine release from the pulmonary parasympathetic nerves. M2 receptors are dysfunctional in antigen-challenged guinea pigs, causing increased vagally mediated bronchoconstriction. Dysfunction of these M2 receptors is due to eosinophil major basic protein, which is an antagonist for M2 receptors. Histamine-induced bronchoconstriction is composed of a vagal reflex in addition to its direct effect on airway smooth muscle. Because hyperreactivity to histamine is seen in antigen-challenged animals, we hypothesized that hyperreactivity to histamine may be due to increased vagally mediated bronchoconstriction caused by dysfunction of M2 receptors. In anesthetized, antigen-challenged guinea pigs, histamine-induced bronchoconstriction was greater than that in control guinea pigs. After vagotomy or atropine treatment, the response to histamine in antigen-challenged animals was the same as that in control animals. In antigen-challenged animals, blockade of eosinophil influx into the airways or neutralization of eosinophil major basic protein prevented the development of hyperreactivity to histamine. Thus hyperreactivity to histamine in antigen- challenged guinea pigs is vagally mediated and dependent on eosinophil major basic protein.
Original language | English (US) |
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Pages (from-to) | L709-L714 |
Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
Volume | 276 |
Issue number | 5 20-5 |
DOIs | |
State | Published - May 1999 |
Externally published | Yes |
Keywords
- Adhesion molecules
- Inflammation
- Major basic protein
- Muscarinic receptors
- Parasympathetic nerves
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology