Mast cell-cholinergic nerve interaction in mouse airways

Letitia A. Weigand, Allen C. Myers, Sonya Meeker, Bradley J. Undem

Research output: Contribution to journalArticlepeer-review

Abstract

We addressed the mechanism by which antigen contracts trachea isolated from actively sensitized mice. Trachea were isolated from mice (C57BL/ 6J) that had been actively sensitized to ovalbumin (OVA). OVA (10 μg ml-1) caused histamine release (∼70% total tissue content), and smooth muscle contraction that was rapid in onset and short-lived (t1/2 < 1 min), reaching approximately 25% of the maximum tissue response. OVA contraction was mimicked by 5-HT, and responses to both OVA and 5-HT were sensitive to 10 μm-ketanserin (5-HT2 receptor antagonist) and strongly inhibited by atropine (1 μM). Epithelial denudation had no effect on the OVA-induced contraction. Histological assessment revealed about five mast cells/tracheal section the vast majority of which contained 5-HT. There were virtually no mast cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit histamine release or contractile responses in trachea isolated from sensitized mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane potential of parasympathetic neurons in mouse tracheal ganglia revealed a ketanserin-sensitive 5-HT-induced depolarization 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-HT2 receptors on parasympathetic cholinergic neurons. This leads to acetylcholine release from nerve terminals, and airway smooth muscle contraction.

Original languageEnglish (US)
Pages (from-to)3355-3362
Number of pages8
JournalJournal of Physiology
Volume587
Issue number13
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Physiology

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