TY - JOUR
T1 - Allergen and ozone exacerbate serotonin-induced increases in airway smooth muscle contraction in a model of childhood asthma
AU - Moore, Brian D.
AU - Hyde, Dallas
AU - Miller, Lisa
AU - Wong, Emily
AU - Frelinger, Jessica
AU - Schelegle, Edward S
PY - 2012/6
Y1 - 2012/6
N2 - 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.
AB - 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.
KW - Air pollution
KW - Airway hyperresponsiveness
KW - Childhood asthma
KW - House dust mite allergen
KW - Rhesus monkeys
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=84862771013&partnerID=8YFLogxK
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U2 - 10.1159/000336835
DO - 10.1159/000336835
M3 - Article
C2 - 22507883
AN - SCOPUS:84862771013
VL - 83
SP - 529
EP - 542
JO - Schweizerische Zeitschrift für Tuberkulose und Pneumonologie. Revue suisse de la tuberculose et de pneumonologie. Rivista svizzera della tubercolosi e della pneumonologia
JF - Schweizerische Zeitschrift für Tuberkulose und Pneumonologie. Revue suisse de la tuberculose et de pneumonologie. Rivista svizzera della tubercolosi e della pneumonologia
SN - 0025-7931
IS - 6
ER -