ArticlePloS one2011
β2-Agonist induced cAMP is decreased in asthmatic airway smooth muscle due to increased PDE4D.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 84 citations in OpenAlex.
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- Rhinovirus C15 Attenuates Relaxation and cAMP Production in Human Airways and Smooth Muscle.American journal of respiratory cell and molecular biology · 2023Article
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- Homeostatic glucocorticoid signaling in airway smooth muscle: A roadmap to asthma pathogenesis.Frontiers in endocrinology · 2022Article
- Inhibition of ABCC1 Decreases cAMP Egress and Promotes Human Airway Smooth Muscle Cell Relaxation.American journal of respiratory cell and molecular biology · 2022Article
- Gut probiotic Lactobacillus rhamnosus attenuates PDE4B-mediated interleukin-6 induced by SARS-CoV-2 membrane glycoprotein.The Journal of nutritional biochemistry · 2021Article
- Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the βFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatmentERJ open research · 2021Article
- Article
- Dexamethasone rescues TGF-β1-mediated βRespiratory research · 2020Article
- Cyclic AMP in dendritic cells: A novel potential target for disease-modifying agents in asthma and other allergic disorders.British journal of pharmacology · 2020Review
- Phosphodiesterase isoforms and cAMP compartments in the development of new therapies for obstructive pulmonary diseases.Current opinion in pharmacology · 2020Review
- Rhinovirus C15 Induces Airway Hyperresponsiveness via Calcium Mobilization in Airway Smooth Muscle.American journal of respiratory cell and molecular biology · 2020Article
- Effects of PDE4 gene polymorphisms on efficacy and adverse drug events of ritodrine therapy in preterm labor patients: a prospective observational study.European journal of clinical pharmacology · 2019Observational
- Transforming Growth Factor-β1 Decreases βAmerican journal of respiratory cell and molecular biology · 2019Article
- Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways.Frontiers in pharmacology · 2019Article
- TGF-β1 Evokes Human Airway Smooth Muscle Cell Shortening and Hyperresponsiveness via Smad3.American journal of respiratory cell and molecular biology · 2018Article
- Epac Function and cAMP Scaffolds in the Heart and Lung.Journal of cardiovascular development and disease · 2018Review
- A pathophysiological role of PDE3 in allergic airway inflammation.JCI insight · 2018Article
- Taste and smell GPCRs in the lung: Evidence for a previously unrecognized widespread chemosensory system.Cellular signalling · 2018Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
objectiveAsthma is associated with airway narrowing in response to bronchoconstricting stimuli and increased airway smooth muscle (ASM) mass. In addition, some studies have suggested impaired β-agonist induced ASM relaxation in asthmatics, but the mechanism is not known.
objectiveTo characterize the potential defect in β-agonist induced cAMP in ASM derived from asthmatic in comparison to non-asthmatic subjects and to investigate its mechanism.
methodsWe examined β(2)-adrenergic (β(2)AR) receptor expression and basal β-agonist and forskolin (direct activator of adenylyl cyclase) stimulated cAMP production in asthmatic cultured ASM (n = 15) and non-asthmatic ASM (n = 22). Based on these results, PDE activity, PDE4D expression and cell proliferation were determined.
resultsIn the presence of IBMX, a pan PDE inhibitor, asthmatic ASM had ∼50% lower cAMP production in response to isoproterenol, albuterol, formoterol, and forskolin compared to non-asthmatic ASM. However when PDE4 was specifically inhibited, cAMP production by the agonists and forskolin was normalized in asthmatic ASM. We then measured the amount and activity of PDE4, and found ∼2-fold greater expression and activity in asthmatic ASM compared to non-asthmatic ASM. Furthermore, inhibition of PDE4 reduced asthmatic ASM proliferation but not that of non-asthmatic ASM.
conclusionDecreased β-agonist induced cAMP in ASM from asthmatics results from enhanced degradation due to increased PDE4D expression. Clinical manifestations of this dysregulation would be suboptimal β-agonist-mediated bronchodilation and possibly reduced control over increasing ASM mass. These phenotypes appear to be "hard-wired" into ASM from asthmatics, as they do not require an inflammatory environment in culture to be observed.
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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.