ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Targeting the restricted α-subunit repertoire of airway smooth muscle GABAA receptors augments airway smooth muscle relaxation.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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44 citing papers in PubMed, 63 citations in OpenAlex.
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- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 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
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- Ginger metabolites and metabolite-inspired synthetic products modulate intracellular calcium and relax airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Identification and Quantification of MIDD0301 Metabolites.Current drug metabolism · 2021Article
- Neuroimmune Pathophysiology in Asthma.Frontiers in cell and developmental biology · 2021Review
- Nebulized MIDD0301 Reduces Airway Hyperresponsiveness in Moderate and Severe Murine Asthma Models.ACS pharmacology & translational science · 2020Article
- Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity.American journal of respiratory cell and molecular biology · 2020Article
- Alterations in Serum-Free Amino Acid Profiles in Childhood Asthma.International journal of environmental research and public health · 2020Article
- The Effects of pH on the Structure and Bioavailability of Imidazobenzodiazepine-3-Carboxylate MIDD0301.Molecular pharmaceutics · 2020Article
- Stress Reduction Techniques for Health Care Providers Dealing With Severe Coronavirus Infections (SARS, MERS, and COVID-19): A Rapid Review.Frontiers in psychology · 2020Review
- MIDD0301 - A first-in-class anti-inflammatory asthma drug targets GABABasic & clinical pharmacology & toxicology · 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
- GABAAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
The prevalence of asthma has taken on pandemic proportions. Since this disease predisposes patients to severe acute airway constriction, novel mechanisms capable of promoting airway smooth muscle relaxation would be clinically valuable. We have recently demonstrated that activation of endogenous airway smooth muscle GABA(A) receptors potentiates β-adrenoceptor-mediated relaxation, and molecular analysis of airway smooth muscle reveals that the α-subunit component of these GABA(A) receptors is limited to the α(4)- and α(5)-subunits. We questioned whether ligands with selective affinity for these GABA(A) receptors could promote relaxation of airway smooth muscle. RT-PCR analysis of GABA(A) receptor subunits was performed on RNA isolated by laser capture microdissection from human and guinea pig airway smooth muscle. Membrane potential and chloride-mediated current were measured in response to GABA(A) subunit-selective agonists in cultured human airway smooth muscle cells. Functional relaxation of precontracted guinea pig tracheal rings was assessed in the absence and presence of the α(4)-subunit-selective GABA(A) receptor agonists: gaboxadol, taurine, and a novel 8-methoxy imidazobenzodiazepine (CM-D-45). Only messenger RNA encoding the α(4)- and α(5)-GABA(A) receptor subunits was identified in RNA isolated by laser capture dissection from guinea pig and human airway smooth muscle tissues. Activation of airway smooth muscle GABA(A) receptors with agonists selective for these subunits resulted in appropriate membrane potential changes and chloride currents and promoted relaxation of airway smooth muscle. In conclusion, selective subunit targeting of endogenous airway smooth muscle-specific GABA(A) receptors may represent a novel therapeutic option for patients in severe bronchospasm.
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