Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors

Nicholas G. Jendzjowsky, Arijit Roy, Nicole O. Barioni, Margaret M. Kelly, Francis H. Y. Green, Christopher N. Wyatt, Richard L. Pye, Luana Tenorio-Lopes and Richard J. A. Wilson ()
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Nicholas G. Jendzjowsky: University of Calgary
Arijit Roy: University of Calgary
Nicole O. Barioni: University of Calgary
Margaret M. Kelly: University of Calgary
Francis H. Y. Green: University of Calgary
Christopher N. Wyatt: Wright State University
Richard L. Pye: Wright State University
Luana Tenorio-Lopes: University of Calgary
Richard J. A. Wilson: University of Calgary

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract Asthma accounts for 380,000 deaths a year. Carotid body denervation has been shown to have a profound effect on airway hyper-responsiveness in animal models but a mechanistic explanation is lacking. Here we demonstrate, using a rat model of asthma (OVA-sensitized), that carotid body activation during airborne allergic provocation is caused by systemic release of lysophosphatidic acid (LPA). Carotid body activation by LPA involves TRPV1 and LPA-specific receptors, and induces parasympathetic (vagal) activity. We demonstrate that this activation is sufficient to cause acute bronchoconstriction. Moreover, we show that prophylactic administration of TRPV1 (AMG9810) and LPA (BrP-LPA) receptor antagonists prevents bradykinin-induced asthmatic bronchoconstriction and, if administered following allergen exposure, reduces the associated respiratory distress. Our discovery provides mechanistic insight into the critical roles of carotid body LPA receptors in allergen-induced respiratory distress and suggests alternate treatment options for asthma.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06189-y

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DOI: 10.1038/s41467-018-06189-y

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