ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Airway epithelium is a predominant source of endogenous airway GABA and contributes to relaxation of airway smooth muscle tone.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Article
- Bronchial epithelial and airway smooth muscle cell interactions in health and disease.Heliyon · 2023Review
- Imidazobenzodiazepine PI320 Relaxes Mouse Peripheral Airways by Inhibiting Calcium Mobilization.American journal of respiratory cell and molecular biology · 2022Article
- Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- B cell-derived GABA elicits IL-10Nature · 2021Article
- Reticular Basement Membrane Thickness Is Associated with Growth- and Fibrosis-Promoting Airway Transcriptome Profile-Study in Asthma Patients.International journal of molecular sciences · 2021Article
- The short-chain free fatty acid receptor FFAR3 is expressed and potentiates contraction in human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Agonism of the TMEM16A calcium-activated chloride channel modulates airway smooth muscle tone.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Novel Expression of GABAA Receptors on Resistance Arteries That Modulate Myogenic Tone.Journal of vascular research · 2020Article
- Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation.Scientific reports · 2019Article
- Relaxant Action of Diclofenac Sodium on Mouse Airway Smooth Muscle.Frontiers in pharmacology · 2019Article
- Anoctamin Channels in Human Myometrium: A Novel Target for Tocolysis.Reproductive sciences (Thousand Oaks, Calif.) · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Transforming Growth Factor β1 Function in Airway Remodeling and Hyperresponsiveness. The Missing Link?American journal of respiratory cell and molecular biology · 2017Review
- Optimization of substituted imidazobenzodiazepines as novel asthma treatments.European journal of medicinal chemistry · 2017Article
- Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma.American journal of respiratory and critical care medicine · 2016Observational
- Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Article
- A microfluidics-based in vitro model of the gastrointestinal human-microbe interface.Nature communications · 2016Article
- Glycogen synthase kinase-3β modulation of glucocorticoid responsiveness in COPD.American journal of physiology. Lung cellular and molecular physiology · 2015Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Chronic obstructive pulmonary disease and asthma are characterized by hyperreactive airway responses that predispose patients to episodes of acute airway constriction. Recent studies suggest a complex paradigm of GABAergic signaling in airways that involves GABA-mediated relaxation of airway smooth muscle. However, the cellular source of airway GABA and mechanisms regulating its release remain unknown. We questioned whether epithelium is a major source of GABA in the airway and whether the absence of epithelium-derived GABA contributes to greater airway smooth muscle force. Messenger RNA encoding glutamic acid decarboxylase (GAD) 65/67 was quantitatively measured in human airway epithelium and smooth muscle. HPLC quantified GABA levels in guinea pig tracheal ring segments under basal or stimulated conditions with or without epithelium. The role of endogenous GABA in the maintenance of an acetylcholine contraction in human airway and guinea pig airway smooth muscle was assessed in organ baths. A 37.5-fold greater amount of mRNA encoding GAD 67 was detected in human epithelium vs. airway smooth muscle cells. HPLC confirmed that guinea pig airways with intact epithelium have a higher constitutive elution of GABA under basal or KCl-depolarized conditions compared with epithelium-denuded airway rings. Inhibition of GABA transporters significantly suppressed KCl-mediated release of GABA from epithelium-intact airways, but tetrodotoxin was without effect. The presence of intact epithelium had a significant GABAergic-mediated prorelaxant effect on the maintenance of contractile tone. Airway epithelium is a predominant cellular source of endogenous GABA in the airway and contributes significant prorelaxant GABA effects on airway smooth muscle force.
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