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Preventing Acute Asthmatic Symptoms by Targeting a Neuronal Mechanism Involving Carotid Body Lysophosphatidic Acid Receptors

By Nicholas G. Jendzjowsky, Arijit Roy, Nicole O Barioni, Margaret M Kelly, Francis HY Green, Christopher N. Wyatt, Richard L. Pye, Luana Tenorio Lopes and Richard A Wilson

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

Topics: Medical Cell Biology, Medical Neurobiology, Medical Physiology, Medical Sciences, Medicine and Health Sciences, Neurosciences, Physiological Processes
Publisher: CORE Scholar
Year: 2018
OAI identifier: oai:corescholar.libraries.wright.edu:ncbp-2146
Provided by: CORE
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