TY - JOUR
T1 - Antigen-induced hyperreactivity to histamine
T2 - Role of the vagus nerves and eosinophils
AU - Costello, Richard W.
AU - Evans, Christopher M.
AU - Yost, Bethany L.
AU - Belmonte, Kristen E.
AU - Gleich, Gerald J.
AU - Jacoby, David B.
AU - Fryer, Allison D.
N1 - Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 1999/5
Y1 - 1999/5
N2 - 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.
AB - 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.
KW - Adhesion molecules
KW - Inflammation
KW - Major basic protein
KW - Muscarinic receptors
KW - Parasympathetic nerves
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U2 - 10.1152/ajplung.1999.276.5.l709
DO - 10.1152/ajplung.1999.276.5.l709
M3 - Article
C2 - 10330026
AN - SCOPUS:0032968333
VL - 276
SP - L709-L714
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 1040-0605
IS - 5 20-5
ER -