Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma

Brian D. Moore, Dallas Hyde, Lisa Miller, Emily Wong, Jessica Frelinger, Edward S Schelegle

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Serotonin (5-HT) modulates cholinergic neurotransmission and exacerbates airway smooth muscle (ASM) contraction in normal animal and nonasthmatic human tissue. Exposure to house dust mite allergen (HDMA) and ozone (O 3) leads to airway hyperreactivity and 5-HT-positive cells in the airway epithelium of infant rhesus monkeys. Research shows that concomitant exposure in allergic animals has an additive effect on airway hyperreactivity. Objectives: In this study, the hypothesis is that the exposure of allergic infant rhesus monkeys to HDMA, O 3 and in combination, acting through 5-HT receptors, enhances 5-HT modulation of postganglionic cholinergic ASM contraction. Methods: Twenty-four HDMA-sensitized infant monkeys were split into 4 groups at the age of 1 month, and were exposed to filtered air (FA), HDMA, O 3 or in combination (HDMA+O 3). At the age of 6 months, airway rings were harvested and postganglionic, and parasympathetic-mediated ASM contraction was evaluated using electrical-field stimulation (EFS). Results: 5-HT exacerbated the EFS response within all exposure groups, but had no effect in the FA group. 5-HT 2, 5-HT 3 and 5-HT 4 receptor agonists exacerbated the response. 5-HT concentration-response curves performed after incubation with specific receptor antagonists confirmed the involvement of 5-HT 2, 5-HT 3 and 5-HT 4 receptors. Conversely, a 5-HT 1 receptor agonist attenuated the tension across all groups during EFS, and in ASM contracted via exogenous acetylcholine. Conclusions: HDMA, O 3 and HDMA+O 3 exposure in a model of childhood allergic asthma enhances 5-HT exacerbation of EFS-induced ASM contraction through 5-HT 2, 5-HT 3 and 5-HT 4 receptors. A nonneurogenic inhibitory pathway exists, unaffected by exposure, mediated by 5-HT 1 receptors located on ASM.

Original languageEnglish (US)
Pages (from-to)529-542
Number of pages14
JournalRespiration
Volume83
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Air pollution
  • Airway hyperresponsiveness
  • Childhood asthma
  • House dust mite allergen
  • Rhesus monkeys
  • Serotonin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint Dive into the research topics of 'Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma'. Together they form a unique fingerprint.

  • Cite this