ArticleThe Journal of clinical investigation2007
Crosstalk between Gi and Gq/Gs pathways in airway smooth muscle regulates bronchial contractility and relaxation.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 66 citations in OpenAlex.
- Regulatory haplotypes in ARG1 are associated with altered bronchodilator response.American journal of respiratory and critical care medicine · 2011Trial
- Biased Orthosteric Agonism and Allosteric Modulation: Emerging Strategies for Developing New Class of β-Agonists for Obstructive Airway Diseases.American journal of respiratory cell and molecular biology · 2025Review
- Hippocampal astrocytes induce sex-dimorphic effects on memory.Cell reports · 2024Article
- S-nitrosylation is required for βMolecular cell · 2022Article
- Ciliary Type III Adenylyl Cyclase in the VMH Is Crucial for High-Fat Diet-Induced Obesity Mediated by Autophagy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- NaJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Modulation of airway hyperresponsiveness by rhinovirus exposure.Respiratory research · 2018Review
- A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling.BMC biology · 2018Article
- Taste and smell GPCRs in the lung: Evidence for a previously unrecognized widespread chemosensory system.Cellular signalling · 2018Review
- Coupling of Airway Smooth Muscle Bitter Taste Receptors to Intracellular Signaling and Relaxation Is via GAmerican journal of respiratory cell and molecular biology · 2017Article
- Shared genetic variants between serum levels of high-density lipoprotein cholesterol and wheezing in a cohort of children from Cyprus.Italian journal of pediatrics · 2016Article
- Cryopreserved Human Precision-Cut Lung Slices as a Bioassay for Live Tissue Banking. A Viability Study of Bronchodilation with Bitter-Taste Receptor Agonists.American journal of respiratory cell and molecular biology · 2016Article
- Targeted transgenesis identifies Gαs as the bottleneck in β2-adrenergic receptor cell signaling and physiological function in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Loss of regulator of G protein signaling 5 promotes airway hyperresponsiveness in the absence of allergic inflammation.The Journal of allergy and clinical immunology · 2014Article
- The pharmacological rationale for combining muscarinic receptor antagonists and β-adrenoceptor agonists in the treatment of airway and bladder disease.Current opinion in pharmacology · 2014Review
- A genome-wide association study of bronchodilator response in asthmatics.The pharmacogenomics journal · 2014Article
- TAS2R activation promotes airway smooth muscle relaxation despite β(2)-adrenergic receptor tachyphylaxis.American journal of physiology. Lung cellular and molecular physiology · 2012Article
- Regulator of G-protein signaling-5 inhibits bronchial smooth muscle contraction in severe asthma.American journal of respiratory cell and molecular biology · 2012Article
- Respiratory syncytial virus reverses airway hyperresponsiveness to methacholine in ovalbumin-sensitized mice.PloS one · 2012Article
- G Protein βγ-subunit signaling mediates airway hyperresponsiveness and inflammation in allergic asthma.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Receptor-mediated airway smooth muscle (ASM) contraction via G(alphaq), and relaxation via G(alphas), underlie the bronchospastic features of asthma and its treatment. Asthma models show increased ASM G(alphai) expression, considered the basis for the proasthmatic phenotypes of enhanced bronchial hyperreactivity to contraction mediated by M(3)-muscarinic receptors and diminished relaxation mediated by beta(2)-adrenergic receptors (beta(2)ARs). A causal effect between G(i) expression and phenotype has not been established, nor have mechanisms whereby G(i) modulates G(q)/G(s) signaling. To delineate isolated effects of altered G(i), transgenic mice were generated overexpressing G(alphai2) or a G(alphai2) peptide inhibitor in ASM. Unexpectedly, G(alphai2) overexpression decreased contractility to methacholine, while G(alphai2) inhibition enhanced contraction. These opposite phenotypes resulted from different crosstalk loci within the G(q) signaling network: decreased phospholipase C and increased PKCalpha, respectively. G(alphai2) overexpression decreased beta(2)AR-mediated airway relaxation, while G(alphai2) inhibition increased this response, consistent with physiologically relevant coupling of this receptor to both G(s) and G(i). IL-13 transgenic mice (a model of asthma), which developed increased ASM G(alphai), displayed marked increases in airway hyperresponsiveness when G(alphai) function was inhibited. Increased G(alphai) in asthma is therefore a double-edged sword: a compensatory event mitigating against bronchial hyperreactivity, but a mechanism that evokes beta-agonist resistance. By selective intervention within these multipronged signaling modules, advantageous G(s)/G(q) activities could provide new asthma therapies.
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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.