ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Selective targeting of the α5-subunit of GABAA receptors relaxes airway smooth muscle and inhibits cellular calcium handling.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Airway smooth muscle in contractility and remodeling of asthma: potential drug target mechanisms.Expert opinion on therapeutic targets · 2023Article
- Perspectives on precision cut lung slices-powerful tools for investigation of mechanisms and therapeutic targets in lung diseases.Frontiers in pharmacology · 2023Review
- Imidazobenzodiazepine PI320 Relaxes Mouse Peripheral Airways by Inhibiting Calcium Mobilization.American journal of respiratory cell and molecular biology · 2022Article
- Anxiolytics for Bronchodilation: Refinements to GABAAmerican journal of respiratory cell and molecular biology · 2022Article
- Comparative pharmacodynamic and pharmacokinetic study of MIDD0301 and its (S) enantiomer.Drug development research · 2022Article
- Development of Inhaled GABAACS pharmacology & translational science · 2022Article
- Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models.ACS pharmacology & translational science · 2020Article
- Upregulation of airway smooth muscle calcium-sensing receptor by low-molecular-weight hyaluronan.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
- Non-sedating benzodiazepines cause paralysis and tissue damage in the parasitic blood fluke Schistosoma mansoni.PLoS neglected tropical diseases · 2019Article
- Argon reduces the pulmonary vascular tone in rats and humans by GABA-receptor activation.Scientific reports · 2019Article
- A novel GABAAmerican journal of physiology. Lung cellular and molecular physiology · 2019Article
- A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAMolecular pharmaceutics · 2018Article
- Molecular Characterization of GABA-A Receptor Subunit Diversity within Major Peripheral Organs and Their Plasticity in Response to Early Life Psychosocial Stress.Frontiers in molecular neuroscience · 2018Article
- Ion channels of the lung and their role in disease pathogenesis.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- Influenza virus infection alters ion channel function of airway and alveolar cells: mechanisms and physiological sequelae.American journal of physiology. Lung cellular and molecular physiology · 2017Review
- GABAAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAMolecular pharmaceutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The clinical need for novel bronchodilators for the treatment of bronchoconstrictive diseases remains a major medical issue. Modulation of airway smooth muscle (ASM) chloride via GABAA receptor activation to achieve relaxation of precontracted ASM represents a potentially beneficial therapeutic option. Since human ASM GABAA receptors express only the α4- and α5-subunits, there is an opportunity to selectively target ASM GABAA receptors to improve drug efficacy and minimize side effects. Recently, a novel compound (R)-ethyl8-ethynyl-6-(2-fluorophenyl)-4-methyl-4H-benzo[f]imidazo[1,5-a][1,4] diazepine-3-carboxylate (SH-053-2'F-R-CH3) with allosteric selectivity for α5-subunit containing GABAA receptors has become available. We questioned whether this novel GABAA α5-selective ligand relaxes ASM and affects intracellular calcium concentration ([Ca(2+)]i) regulation. Immunohistochemical staining localized the GABAA α5-subunit to human ASM. The selective GABAA α5 ligand SH-053-2'F-R-CH3 relaxes precontracted intact ASM; increases GABA-activated chloride currents in human ASM cells in voltage-clamp electrophysiology studies; and attenuates bradykinin-induced increases in [Ca(2+)]i, store-operated Ca(2+) entry, and methacholine-induced Ca(2+) oscillations in peripheral murine lung slices. In conclusion, selective subunit targeting of endogenous α5-subunit containing GABAA receptors on ASM may represent a novel therapeutic option to treat severe bronchospasm.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.