title: Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, and Respiratory Diseases Unit, California National Primate Research Center, University of California - Davis, Davis, CA 95616-8732, USA. brimoore@ucdavis.edu
authors.forename: Brian D
authors.initials: BD
authors.lastname: Moore
authors.forename: Dallas
authors.initials: D
authors.lastname: Hyde
authors.forename: Lisa
authors.initials: L
authors.lastname: Miller
authors.forename: Emily
authors.initials: E
authors.lastname: Wong
authors.forename: Jessica
authors.initials: J
authors.lastname: Frelinger
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D007428:Intradermal Tests; D008253:Macaca mulatta; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology; D010126:Ozone / Q000276:immunology / Q000494:pharmacology*; D039981:Pyroglyphidae / Q000276:immunology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000627:therapeutic use
chemical_list: D000485:Allergens; D012702:Serotonin Antagonists; D012701:Serotonin; D010126:Ozone