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Mast cell‐cholinergic nerve interaction in mouse airway
Author(s) -
Weigand Letitia,
Meeker Sonya,
Myers Allen C,
Undem Bradley J
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.622.10
Subject(s) - histamine , ovalbumin , ketanserin , contraction (grammar) , cholinergic , mast cell , medicine , acetylcholine , endocrinology , methacholine , depolarization , chemistry , atropine , histamine h1 receptor , methysergide , biology , receptor , serotonin , antagonist , immunology , 5 ht receptor , lung , antigen , respiratory disease
Trachea were isolated from mice (C57BL/6J) that had been actively sensitized to ovalbumin (OVA) via 3 i.p. injections. OVA (10µg/mL) caused histamine release (≈50% total tissue content), and smooth muscle contraction that was rapid in onset and short‐lived (t ½ =<1 minute), reaching 26.5±2.2% of the maximum response to methacholine (n=18). OVA contraction was mimicked by 5‐hydroxytryptamine (5‐HT), and responses to both OVA and 5‐HT were sensitive to 10 µM‐ketanserin (5‐HT 2 receptor antagonist, n=5), and was strongly inhibited by atropine (1 µM, n=4). Epithelial denudation had little effect on OVA‐induced contraction (n=7). OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell‐deficient ( sash ‐/‐ ) mice (n=3). Intracellular recordings of cholinergic neurons in mouse tracheal ganglia revealed a ketanserin‐sensitive 5‐HT‐induced depolarization (6.8 mV, n=6), and similar depolarization in response to OVA challenge. These data support the hypothesis that antigen‐induced contraction of mouse trachea is epithelium‐independent, and requires mast cell‐derived 5‐HT to activate 5‐HT 2 receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals and airway smooth muscle contraction. This work was supported by the NIH.