ArticleProceedings of the National Academy of Sciences of the United States of America2000
Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 155 citations in OpenAlex.
- The effect of the novel phosphodiesterase-4 inhibitor MEM 1414 on the allergen induced responses in mild asthma.BMC pulmonary medicine · 2014Trial
- Phosphodiesterase 4B inhibition: a potential novel strategy for treating pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Theophylline-Induced Relaxation Is Enhanced after Testosterone Treatment via Increased KInternational journal of molecular sciences · 2023Article
- Pathophysiology, Therapeutic Targets, and Future Therapeutic Alternatives in COPD: Focus on the Importance of the Cholinergic System.Biomolecules · 2023Review
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- Clinical Implication of Phosphodiesterase-4-Inhibition.International journal of molecular sciences · 2022Review
- Homeostatic glucocorticoid signaling in airway smooth muscle: A roadmap to asthma pathogenesis.Frontiers in endocrinology · 2022Article
- Transforming Growth Factor-β1 Decreases βAmerican journal of respiratory cell and molecular biology · 2019Article
- A pathophysiological role of PDE3 in allergic airway inflammation.JCI insight · 2018Article
- Aberrant DNA Methylation of Phosphodiesterase [corrected] 4D Alters Airway Smooth Muscle Cell Phenotypes.American journal of respiratory cell and molecular biology · 2016Article
- MEK Inhibitors Reverse cAMP-Mediated Anxiety in Zebrafish.Chemistry & biology · 2015Article
- Phosphodiesterase inhibitors as therapeutics for traumatic brain injury.Current pharmaceutical design · 2015Review
- Article
- Cyclic nucleotide phosphodiesterases: important signaling modulators and therapeutic targets.Oral diseases · 2015Review
- Clinical and molecular genetics of the phosphodiesterases (PDEs).Endocrine reviews · 2014Review
- Advances in targeting cyclic nucleotide phosphodiesterases.Nature reviews. Drug discovery · 2014Review
- Structural basis for the design of selective phosphodiesterase 4B inhibitors.Cellular signalling · 2014Article
- Effects of inactivated Bordetella pertussis on phosphodiesterase in the lung of ovalbumin sensitized and challenged rats.Pulmonary medicine · 2014Article
- PDE4 as a target for cognition enhancement.Expert opinion on therapeutic targets · 2013Review
- Quercetin acutely relaxes airway smooth muscle and potentiates β-agonist-induced relaxation via dual phosphodiesterase inhibition of PLCβ and PDE4.American journal of physiology. Lung cellular and molecular physiology · 2013Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Muscarinic cholinergic signaling plays an essential role in the control of the normal airway functions and in the development of pulmonary pathologies including asthma. In this paper we demonstrate that the airways of mice deficient in a cAMP-specific phosphodiesterase (PDE4D) are no longer responsive to cholinergic stimulation. Airway hyperreactivity that follows exposure to antigen was also abolished in PDE4D(-/-) mice, despite an apparently normal lung inflammatory infiltration. The loss of cholinergic responsiveness was specific to the airway, not observed in the heart, and was associated with a loss of signaling through muscarinic receptors with an inability to decrease cAMP accumulation. These findings demonstrate that the PDE4D gene plays an essential role in cAMP homeostasis and cholinergic stimulation of the airway, and in the development of hyperreactivity. In view of the therapeutic potentials of PDE4 inhibitors, our findings provide the rationale for novel strategies that target a single PDE isoenzyme.
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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.