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.
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Authors | Brian D Moore, Dallas Hyde, Lisa Miller, Emily Wong, Jessica Frelinger, Edward S Schelegle |
Journal | Respiration; international review of thoracic diseases
(Respiration)
Vol. 83
Issue 6
Pg. 529-42
( 2012)
ISSN: 1423-0356 [Electronic] Switzerland |
PMID | 22507883
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 S. Karger AG, Basel. |
Chemical References |
- Allergens
- Serotonin Antagonists
- Serotonin
- Ozone
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Topics |
- Allergens
(immunology)
- Animals
- Asthma
(immunology)
- Disease Models, Animal
- Disease Progression
- Dose-Response Relationship, Drug
- Intradermal Tests
- Macaca mulatta
- Muscle Contraction
(physiology)
- Muscle, Smooth
(physiology)
- Ozone
(immunology, pharmacology)
- Pyroglyphidae
(immunology)
- Serotonin
(physiology)
- Serotonin Antagonists
(therapeutic use)
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