ArticleMolecular pharmacology2016
Interdicting Gq Activation in Airway Disease by Receptor-Dependent and Receptor-Independent Mechanisms.
Article in Molecular pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Pharmacological Gq targeting prevents asthmatic airway remodeling.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- GQ style: a multipronged therapeutic approach to pulmonary arterial hypertension.Pflugers Archiv : European journal of physiology · 2025Article
- Going Rogue: Mechanisms, Regulation, and Roles of Mutationally Activated GMolecular pharmacology · 2024Review
- GRespiratory research · 2024Review
- Identification of sulfakinin receptor regulating feeding behavior and hemolymph trehalose homeostasis in the silkworm, Bombyx mori.Scientific reports · 2024Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- The Bacterial GJournal of chemical ecology · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Therapeutic Approaches for Chronic Obstructive Pulmonary Disease (COPD) Exacerbations.Pathogens (Basel, Switzerland) · 2022Review
- Epinephrine evokes shortening of human airway smooth muscle cells following βAmerican journal of physiology. Lung cellular and molecular physiology · 2022Article
- Lipopeptide Pepducins as Therapeutic Agents.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Targeting Oncogenic GαCancers · 2021Review
- Diacylglycerol Kinase Inhibition Reduces Airway Contraction by Negative Feedback Regulation of Gq-Signaling.American journal of respiratory cell and molecular biology · 2021Article
- Label-Free Investigations on the G Protein Dependent Signaling Pathways of Histamine Receptors.International journal of molecular sciences · 2021Article
- Macrocyclic Gq Protein Inhibitors FR900359 and/or YM-254890-Fit for Translation?ACS pharmacology & translational science · 2021Article
- Allosteric Modulator Leads Hiding in Plain Site: Developing Peptide and Peptidomimetics as GPCR Allosteric Modulators.Frontiers in chemistry · 2021Review
- RGS4 promotes allergen- and aspirin-associated airway hyperresponsiveness by inhibiting PGE2 biosynthesis.The Journal of allergy and clinical immunology · 2020Article
- Targeting of G-protein coupled receptors in sepsis.Pharmacology & therapeutics · 2020Review
- Heterotrimeric GThe Journal of biological chemistry · 2020Review
- Neutrophil Signaling That Challenges Dogmata of G Protein-Coupled Receptor Regulated Functions.ACS pharmacology & translational science · 2020Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Gαqβγ heterotrimer (Gq), an important mediator in the pathology of airway disease, plays a central role in bronchoconstriction and airway remodeling, including airway smooth muscle growth and inflammation. Current therapeutic strategies to treat airway disease include the use of muscarinic and leukotriene receptor antagonists; however, these pharmaceuticals demonstrate a limited clinical efficacy as multiple Gq-coupled receptor subtypes contribute to these pathologies. Thus, broadly inhibiting the activation of Gq may be an advantageous therapeutic approach. Here, we investigated the effects of broadly inhibiting Gq activation in vitro and ex vivo using receptor-dependent and receptor-independent strategies. P4pal-10 is a protease activated receptor 4-derived pepducin that exhibits efficacy toward multiple Gq-coupled receptors. Mechanistic studies demonstrated that P4pal-10 selectively inhibits all G protein coupling to several Gq-coupled receptors, including protease activated receptor 1, muscarinic acetylcholine M3, and histamine H1 receptors, while demonstrating no direct effect on Gq. We also evaluated the ability of FR900359, also known as UBO-QIC, to directly inhibit Gq activation. FR900359 inhibited spontaneous Gαq nucleotide exchange, while having little effect on Gαsβγ, Gαiβγ, or Gα12/13βγ heterotrimer activity. Both P4pal-10 and FR900359 inhibited Gq-mediated intracellular signaling and primary human airway smooth muscle growth, whereas only FR900359 effectively interdicted agonist-promoted airway contraction in human precision cut lung slices. These studies serve as a proof of concept that the broad-based inhibition of Gq activation may be a useful therapeutic approach to treat multiple common pathologies of airway disease.
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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.