ArticleAmerican journal of respiratory cell and molecular biology2016
Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice.
Article in American journal of respiratory cell and molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Qualitative beta-2-adrenoceptor signaling in the regulation of human airway epithelia mucin and cytokine production.Respiratory research · 2026Article
- [Mendelian Randomization Analysis of Potential Molecular Targets for Type 2 Airway Inflammatory Diseases].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- 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
- Identification of a β-arrestin-biased negative allosteric modulator for the βProceedings of the National Academy of Sciences of the United States of America · 2023Article
- In silico identification of a βProceedings of the National Academy of Sciences of the United States of America · 2022Article
- PD 102807 Induces M3 mAChR-Dependent GRK-/Arrestin-Biased Signaling in Airway Smooth Muscle Cells.American journal of respiratory cell and molecular biology · 2022Article
- βBritish journal of pharmacology · 2022Article
- Can GPCRs Be Targeted to Control Inflammation in Asthma?Advances in experimental medicine and biology · 2021Article
- Roflumilast Suppresses Adipogenic DifferentiationFrontiers in endocrinology · 2021Article
- Therapeutic Potential of Targeting ß-Arrestin.Frontiers in pharmacology · 2019Review
- Protease-activated receptor-2 signaling through β-arrestin-2 mediates Alternaria alkaline serine protease-induced airway inflammation.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells.American journal of respiratory cell and molecular biology · 2018Article
- A Novel Orally Available Asthma Drug Candidate That Reduces Smooth Muscle Constriction and Inflammation by Targeting GABAMolecular pharmaceutics · 2018Article
- Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Effects of β-blockers on house dust mite-driven murine models pre- and post-development of an asthma phenotype.Pulmonary pharmacology & therapeutics · 2017Article
- Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAMolecular pharmaceutics · 2017Article
- Understanding how long-acting βBritish journal of pharmacology · 2016Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Mice lacking the endogenous β2-adrenoceptor (β2AR) agonist epinephrine (phenylethanolamine N-methyltransferase [PNMT]-knockout mice) are resistant to developing an "asthma-like" phenotype in an ovalbumin sensitization and challenge (Ova S/C) model, and chronic administration of β2AR agonists to PNMT-KO mice restores the phenotype. Based on these and other studies showing differential effects of various β2AR ligands on the asthma phenotype, we have speculated that the permissive effect of endogenous epinephrine and exogenous β2AR agonists on allergic lung inflammation can be explained by qualitative β2AR signaling. The β2AR can signal through at least two pathways: the canonical Gαs-cAMP pathway and a β-arrestin-dependent pathway. Previous studies suggest that β-arrestin-2 is required for allergic lung inflammation. On the other hand, cell-based assays suggest antiinflammatory effects of Gαs-cAMP signaling. This study was designed to test whether the in vitro antiinflammatory effects of phosphodiesterase 4 inhibitors, known to increase intracellular cAMP in multiple airway cell types, attenuate the asthma-like phenotype produced by the β2AR agonists formoterol and salmeterol in vivo in PNMT-KO mice, based on the hypothesis that skewing β2AR signaling toward Gαs-cAMP pathway is beneficial. Airway inflammatory cells, epithelial mucus production, and airway hyperresponsiveness were quantified. In Ova S/C PNMT-KO mice, formoterol and salmeterol restored the asthma-like phenotype comparable to Ova S/C wild-type mice. However, coadministration of either roflumilast or rolipram attenuated this formoterol- or salmeterol-driven phenotype in Ova S/C PNMT-KO. These findings suggest that amplification of β2AR-mediated cAMP by phosphodiesterase 4 inhibitors attenuates the asthma-like phenotype promoted by β-agonists.
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