brp-lpa has been researched along with Asthma* in 1 studies
1 other study(ies) available for brp-lpa and Asthma
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Preventing acute asthmatic symptoms by targeting a neuronal mechanism involving carotid body lysophosphatidic acid receptors.
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: Acrylamides; Animals; Asthma; Bridged Bicyclo Compounds, Heterocyclic; Carotid Body; Disease Models, Animal; Drug Evaluation, Preclinical; Lysophospholipids; Male; Rats, Inbred BN; Rats, Sprague-Dawley; Receptors, Lysophosphatidic Acid; TRPV Cation Channels | 2018 |