ArticleThe Journal of pharmacology and experimental therapeutics2010
Phosphoinositide 3-kinase gamma regulates airway smooth muscle contraction by modulating calcium oscillations.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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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.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Analysis of the Clinical Efficacy and Molecular Mechanism of Xuefu Zhuyu Decoction in the Treatment of COPD Based on Meta-Analysis and Network Pharmacology.Computational and mathematical methods in medicine · 2022Pooled it
- Integrated network pharmacology, molecular docking, and experimental validation to reveal the potential mechanism of Ginsenoside Rg1 on chronic obstructive pulmonary disease.Scientific reports · 2026Article
- miR-146b disrupts the epidermal growth factor receptor/transforming growth factor β receptor profibrotic feedforward loop to inhibit lung fibroblast proliferation and differentiation.The Journal of pharmacology and experimental therapeutics · 2025Article
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- PI3Kγδ inhibition suppresses key disease features in a rat model of asthma.Respiratory research · 2024Article
- Efficacy of Tounongsan decoction on pyogenic liver abscess: network pharmacology and clinical trial validation.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases.Acta pharmaceutica Sinica. B · 2023Review
- Observational
- Review
- Progress in the mechanism and targeted drug therapy for COPD.Signal transduction and targeted therapy · 2020Review
- Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.Drug development and industrial pharmacy · 2020Article
- Human Pulmonary 3D Models For Translational Research.Biotechnology journal · 2018Review
- Phosphoinositide 3-Kinase in Asthma: Novel Roles and Therapeutic Approaches.American journal of respiratory cell and molecular biology · 2017Review
- Article
- Inhibition of PI3K promotes dilation of human small airways in a rho kinase-dependent manner.British journal of pharmacology · 2016Article
- Inhibition of Gαi activity by Gβγ is mediated by PI 3-kinase-γ- and cSrc-dependent tyrosine phosphorylation of Gαi and recruitment of RGS12.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- The expression and relaxant effect of bitter taste receptors in human bronchi.Respiratory research · 2013Article
- Identification of upregulated phosphoinositide 3-kinase γ as a target to suppress breast cancer cell migration and invasion.Biochemical pharmacology · 2013Article
- Pharmacological profile of phosphatidylinositol 3-kinases and related phosphatidylinositols mediating endothelin(A) receptor-operated native TRPC channels in rabbit coronary artery myocytes.British journal of pharmacology · 2012Article
- Targeting phosphoinositide 3-kinase γ in airway smooth muscle cells to suppress interleukin-13-induced mouse airway hyperresponsiveness.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Phosphoinositide 3-kinase gamma (PI3Kgamma) has been implicated in the pathogenesis of asthma, but its mechanism has been considered indirect, through release of inflammatory cell mediators. Because airway smooth muscle (ASM) contractile hyper-responsiveness plays a critical role in asthma, the aim of the present study was to determine whether PI3Kgamma can directly regulate contractility of ASM. Immunohistochemistry staining indicated expression of PI3Kgamma protein in ASM cells of mouse trachea and lung, which was confirmed by Western blot analysis in isolated mouse tracheal ASM cells. PI3Kgamma inhibitor II inhibited acetylcholine (ACh)-stimulated airway contraction of cultured precision-cut mouse lung slices in a dose-dependent manner with 75% inhibition at 10 muM. In contrast, inhibitors of PI3Kalpha, PI3Kbeta, or PI3Kdelta, at concentrations 40-fold higher than their reported IC(50) values for their primary targets, had no effect. It is noteworthy that airways in lung slices pretreated with PI3Kgamma inhibitor II still exhibited an ACh-induced initial contraction, but the sustained contraction was significantly reduced. Furthermore, the PI3Kgamma-selective inhibitor had a small inhibitory effect on the ACh-stimulated initial Ca(2+) transient in ASM cells of mouse lung slices or isolated mouse ASM cells but significantly attenuated the sustained Ca(2+) oscillations that are critical for sustained airway contraction. This report is the first to show that PI3Kgamma directly controls contractility of airways through regulation of Ca(2+) oscillations in ASM cells. Thus, in addition to effects on airway inflammation, PI3Kgamma inhibitors may also exert direct effects on the airway contraction that contribute to pathologic airway hyper-responsiveness.
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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.