© 2015 the American Physiological Society. Asthma is an inflammatory disease of the lung characterized by airways hyper-responsiveness (AHR), inflammation, and mucus hyperproduction. Current main-stream therapies include bronchodilators that relieve bronchoconstriction and inhaled glucocorticoids to reduce inflammation. The small molecule hormone and neurotransmitter serotonin has long been known to be involved in inflammatory processes; however, its precise role in asthma is unknown. We have previously established that activation of serotonin 5-hydroxytryptamine (5-HT)2A receptors has potent anti-inflammatory activity in primary cultures of vascular tissues and in the whole animal in vasculature and gut tissues. The 5-HT2A receptor agonist, (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] is especially potent. In this work, we have examined the effect of (R)-DOI in an established mouse model of allergic asthma. In the ovalbumin mouse model of allergic inflammation, we demonstrate that inhalation of (R)-DOI prevents the development of many key features of allergic asthma, including AHR, mucus hyperproduction, airways inflammation, and pulmonary eosinophil recruitment. Our results highlight a likely role of the 5-HT2 receptors in allergic airways disease and suggest that 5-HT2 receptor agonists may represent an effective and novel small molecule-based therapy for asthma.
Publication Source (Journal or Book title)
American Journal of Physiology - Lung Cellular and Molecular Physiology
Nau, F., Miller, J., Saravia, J., Ahlert, T., Yu, B., Happel, K., Cormier, S., & Nichols, C. (2015). Serotonin 5-HT2 receptor activation prevents allergic asthma in a mouse model. American Journal of Physiology - Lung Cellular and Molecular Physiology, 308 (2), L191-L198. https://doi.org/10.1152/ajplung.00138.2013