ArticleProceedings of the National Academy of Sciences of the United States of America2016
Soluble guanylate cyclase as an alternative target for bronchodilator therapy in asthma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- NO modulates human airway smooth muscle function by altering glucose-6-phosphate dehydrogenase effects on sGC function in asthma.Redox biology · 2026Article
- Inhaled S-nitrosoglutathione in asthma: Airway SCoR2 expression and determinants of human bronchodilator response.The Journal of allergy and clinical immunology · 2026Article
- Key roles of GAPDH, Hsp90, and NO in heme trafficking.Journal of inorganic biochemistry · 2026Review
- Article
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Expression of soluble guanylate cyclase (sGC) and its ability to form a functional heterodimer are crucial for reviving the NO-sGC signaling in PAH.Free radical biology & medicine · 2024Article
- Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery.Respiratory research · 2024Review
- Regional variations in allergen-induced airway inflammation correspond to changes in soluble guanylyl cyclase heme and expression of heme oxygenase-1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Innovative three-dimensional models for understanding mechanisms underlying lung diseases: powerful tools for translational research.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Role of the Coiled-Coil Domain in Allosteric Activity Regulation in Soluble Guanylate Cyclase.Biochemistry · 2023Article
- BAY58-2667 Activates Different Soluble Guanylyl Cyclase Species by Distinct Mechanisms that Indicate Its Principal Target in Cells is the Heme-Free Soluble Guanylyl Cyclase-Heat Shock Protein 90 Complex.Molecular pharmacology · 2023Article
- Perspectives on precision cut lung slices-powerful tools for investigation of mechanisms and therapeutic targets in lung diseases.Frontiers in pharmacology · 2023Review
- New Mechanistic Advances in FcεRI-Mast Cell-Mediated Allergic Signaling.Clinical reviews in allergy & immunology · 2022Review
- New roles for GAPDH, Hsp90, and NO in regulating heme allocation and hemeprotein function in mammals.Biological chemistry · 2022Review
- The differential roles of the two NO-GC isoforms in adjusting airway reactivity.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Inactivation of soluble guanylyl cyclase in living cells proceeds without loss of haem and involves heterodimer dissociation as a common step.British journal of pharmacology · 2022Article
- Review
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- The Challenge of Long-Term Cultivation of Human Precision-Cut Lung Slices.The American journal of pathology · 2022Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Asthma is defined by airway inflammation and hyperresponsiveness, and contributes to morbidity and mortality worldwide. Although bronchodilation is a cornerstone of treatment, current bronchodilators become ineffective with worsening asthma severity. We investigated an alternative pathway that involves activating the airway smooth muscle enzyme, soluble guanylate cyclase (sGC). Activating sGC by its natural stimulant nitric oxide (NO), or by pharmacologic sGC agonists BAY 41-2272 and BAY 60-2770, triggered bronchodilation in normal human lung slices and in mouse airways. Both BAY 41-2272 and BAY 60-2770 reversed airway hyperresponsiveness in mice with allergic asthma and restored normal lung function. The sGC from mouse asthmatic lungs displayed three hallmarks of oxidative damage that render it NO-insensitive, and identical changes to sGC occurred in human lung slices or in human airway smooth muscle cells when given chronic NO exposure to mimic the high NO in asthmatic lung. Our findings show how allergic inflammation in asthma may impede NO-based bronchodilation, and reveal that pharmacologic sGC agonists can achieve bronchodilation despite this loss.
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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.