ArticleJournal of cellular and molecular medicine2011
Epac as a novel effector of airway smooth muscle relaxation.
Article in Journal of cellular and molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 72 citations in OpenAlex.
- Long-acting βRespiratory research · 2025Article
- Respiratory Ciliary Beat Frequency in COPD: Balancing Oxidative Stress and Pharmacological Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Modulation of fast sodium current in airway smooth muscle cells by exchange protein directly activated by cAMP.American journal of physiology. Cell physiology · 2024Article
- Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.The Journal of clinical investigation · 2023Article
- Perspectives of PDE inhibitor on treating idiopathic pulmonary fibrosis.Frontiers in pharmacology · 2023Review
- Airway smooth muscle and airway hyperresponsiveness in asthma: mechanisms of airway smooth muscle dysfunction.Minerva medica · 2022Article
- Autocrine regulation of airway smooth muscle contraction by diacylglycerol kinase.Journal of cellular physiology · 2022Article
- Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RGS proteins, GRKs, and beta-arrestins modulate G protein-mediated signaling pathways in asthma.Pharmacology & therapeutics · 2021Review
- The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways.Journal of inflammation research · 2021Article
- Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.British journal of pharmacology · 2020Review
- Integration of Rap1 and Calcium Signaling.International journal of molecular sciences · 2020Review
- Disruption of AKAP-PKA Interaction Induces Hypercontractility With Concomitant Increase in Proliferation Markers in Human Airway Smooth Muscle.Frontiers in cell and developmental biology · 2020Article
- Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice.Respiratory research · 2019Article
- Selective inhibition of histamine-evoked CaCell calcium · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Epac Function and cAMP Scaffolds in the Heart and Lung.Journal of cardiovascular development and disease · 2018Review
- Prostaglandin EMolecular pharmacology · 2017Article
- Calcium/calmodulin-dependent kinase 2 mediates Epac-induced spontaneous transient outward currents in rat vascular smooth muscle.The Journal of physiology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Dysfunctional regulation of airway smooth muscle tone is a feature of obstructive airway diseases such as asthma and chronic obstructive pulmonary disease. Airway smooth muscle contraction is directly associated with changes in the phosphorylation of myosin light chain (MLC), which is increased by Rho and decreased by Rac. Although cyclic adenosine monophosphate (cAMP)-elevating agents are believed to relieve bronchoconstriction mainly via activation of protein kinase A (PKA), here we addressed the role of the novel cAMP-mediated exchange protein Epac in the regulation of airway smooth muscle tone. Isometric tension measurements showed that specific activation of Epac led to relaxation of guinea pig tracheal preparations pre-contracted with methacholine, independently of PKA. In airway smooth muscle cells, Epac activation reduced methacholine-induced MLC phosphorylation. Moreover, when Epac was stimulated, we observed a decreased methacholine-induced RhoA activation, measured by both stress fibre formation and pull-down assay whereas the same Epac activation prevented methacholine-induced Rac1 inhibition measured by pull-down assay. Epac-driven inhibition of both methacholine-induced muscle contraction by Toxin B-1470, and MLC phosphorylation by the Rac1-inhibitor NSC23766, were significantly attenuated, confirming the importance of Rac1 in Epac-mediated relaxation. Importantly, human airway smooth muscle tissue also expresses Epac, and Epac activation both relaxed pre-contracted human tracheal preparations and decreased MLC phosphorylation. Collectively, we show that activation of Epac relaxes airway smooth muscle by decreasing MLC phosphorylation by skewing the balance of RhoA/Rac1 activation towards Rac1. Therefore, activation of Epac may have therapeutical potential in the treatment of obstructive airway diseases.
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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.