{"doi":"10.1113/jp281080","title":"PKCε sensing in the carotid body – a new target for asthma?","abstract":"The autonomic nervous system has long been recognized as an important regulator of airway physiology (Barnes, 1986). It communicates with the airway through extensive innervation to the airway smooth muscle, epithelia, glands and vasculature, allowing for constant surveillance of the environment. This surveillance allows for bidirectional communication between the airway and the nervous system, leading to modulation of airway defences, including smooth muscle contraction and mucous secretion. As such, the nervous system has received significant attention as a focal point for modulation of symptoms in airway diseases, including asthma and COPD. For example, in asthma, the airway smooth muscle contracts in an exaggerated fashion. This is often accompanied by copious mucous secretion and airway inflammation. These hallmark features lead to narrowed airways, making it difficult to breathe. As a result, many mainstay therapeutics for asthma aim to minimize airway narrowing by mimicking the sympathetic nervous system (e.g. beta-adrenergic agonists) or inhibiting the actions of the parasympathetic nervous system (e.g. anticholinergics). While our understanding of the role of the autonomic nervous system in modulating airway intrinsic functions in airway health and disease continues to grow, there has been comparatively less emphasis on the consequences of autonomic nervous system cross talk or the manifestations of extra-pulmonary autonomic regulation on airway physiology, especially in the context of asthma. Further, whether extra-pulmonary sites of autonomic regulation can be targeted therapeutically to alleviate asthma symptoms has received limited attention. The carotid bodies act as essential peripheral chemoreceptors that detect arterial oxygen, carbon dioxide and pH. Hypoxia-mediated activation of the carotid bodies can mimic the features of asthma, including exaggerated airway smooth muscle contraction (Denjean et al. 1991). However, carotid body resection is not advised in humans since it decreases the ventilatory drive to hypoxia. These observations suggested that identification of a specific pathway connecting asthma to carotid body activation, and specifically one that spared the oxygen-sensing function, could be targeted therapeutically to possibly alleviate some disease symptoms in asthma. In 2018, such a pathway was discovered in an experimental model of allergic asthma, in which Jendzjowsky and colleagues determined that the carotid bodies were activated by lysophosphatidic acid in rodents sensitized to ovalbumin (Jendzjowsky et al. 2018). Blocking detection of lysophosphatidic acid prevented exaggerated airway narrowing and minimized respiratory distress. However, the exact mechanisms mediating this observation remained unclear. Further, whether the activation of carotid bodies with lysophosphatidic acid was independent of the oxygen-sensing function was not indicated. In a recent issue of the Journal of Physiology, Jendzjowsky and colleagues expanded upon this initial finding to provide new evidence highlighting both a mechanism and pathway that spares the carotid body oxygen-sensing function (Jendzjowsky et al. 2021). Specifically, the authors discovered that several key Th2 cytokines integral to asthma pathogenesis, including IL-13, IL-5 and IL-4, stimulated the carotid body. This finding further emphasized the carotid body as a chemosensor of inflammation. Further, they found that lysophosphatidic acid activated the carotid body through a pathway involving PKCε and TRPV1. Using a heterologous cell system, the authors determined that this pathway likely entailed PKCε-mediated phosphorylation of TRPV1 residues T704 and S502, as mutation of those residues abolished the effect of lysophosphatidic acid on TRPV1-mediated current. To determine whether PKCε-mediated activation of TRPV1 might be responsible for exaggerated airway smooth muscle contraction in asthma, the authors blocked lysophosphatidic acid and PKCε-media","journal":"The Journal of Physiology","year":2020,"id":109282,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":34142,"name":"Leah R. Reznikov","orcid":"0000-0002-4074-9070","position":0,"is_corresponding":true}],"reference_count":4,"raw_metadata":null,"created_at":"2026-07-18T23:12:50.712357Z","pmid":"33215709","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}