ArticleThe Journal of biological chemistry2014
β-Agonist-mediated relaxation of airway smooth muscle is protein kinase A-dependent.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 84 citations in OpenAlex.
- Agonist-specific conformational dynamics at the βBritish journal of pharmacology · 2026Article
- Oxidized phosphatidylcholines inhibit airway smooth muscle β2-adrenergic receptors via protein kinase C.American journal of respiratory cell and molecular biology · 2026Article
- E3 ligase RNF145 regulates airway smooth muscle cell proliferation via the PP2A-p70S6K signaling axis.The Journal of biological chemistry · 2026Article
- Biased signaling of β2-adrenergic receptor in physiological and pathological states.Cellular & molecular biology letters · 2026Review
- 6-Nitrodopamine Potentiates Catecholamine-Induced CaBasic & clinical pharmacology & toxicology · 2026Article
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- Long-acting βRespiratory research · 2025Article
- Ovarian Cancer G protein-coupled receptor-1 signaling bias dictates anti-contractile effect of benzodiazepines on airway smooth muscle.Respiratory research · 2025Article
- TMEM16A Antagonism: Therapeutic Potential with Desensitization of β-Agonist Responsiveness in Asthma.American journal of respiratory cell and molecular biology · 2025Article
- Advancing Obstructive Airway Disease Treatment: Dual PDE3/4 Inhibition as a Therapeutic Strategy.Cells · 2025Review
- β-Ionone facilitates ex vivo airway smooth muscle relaxation via extraocular opsin-3 light receptor activation.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Oxylipin Profiling of Airway Structural Cells Is Unique and Modified by Relevant Stimuli.Journal of proteome research · 2025Article
- Serum cAMP levels are increased in patients with asthma.The Journal of clinical investigation · 2025Article
- Nobiletin, as a Novel PDE4B Inhibitor, Alleviates Asthma Symptoms by Activating the cAMP-PKA-CREB Signaling Pathway.International journal of molecular sciences · 2024Article
- Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Diacylglycerol kinase is a keystone regulator of signaling relevant to the pathophysiology of asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- New phosphodiesterase-4 inhibitors present airways relaxant activity in a guinea pig acute asthma model.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- β-adrenergic receptor regulates embryonic epithelial extensibility through actomyosin inhibition.iScience · 2023Article
- Prorelaxant E-type Prostanoid Receptors Functionally Partition to Different Procontractile Receptors in Airway Smooth Muscle.American journal of respiratory cell and molecular biology · 2023Article
- Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.The Journal of clinical investigation · 2023Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Inhaled β-agonists are effective at reversing bronchoconstriction in asthma, but the mechanism by which they exert this effect is unclear and controversial. PKA is the historically accepted effector, although this assumption is made on the basis of associative and not direct evidence. Recent studies have asserted that exchange protein activated by cAMP (Epac), not PKA, mediates the relaxation of airway smooth muscle (ASM) observed with β-agonist treatment. This study aims to clarify the role of PKA in the prorelaxant effects of β-agonists on ASM. Inhibition of PKA activity via expression of the PKI and RevAB peptides results in increased β-agonist-mediated cAMP release, abolishes the inhibitory effect of isoproterenol on histamine-induced intracellular calcium flux, and significantly attenuates histamine-stimulated MLC-20 phosphorylation. Analyses of ASM cell and tissue contraction demonstrate that PKA inhibition eliminates most, if not all, β-agonist-mediated relaxation of contracted smooth muscle. Conversely, Epac knockdown had no effect on the regulation of contraction or procontractile signaling by isoproterenol. These findings suggest that PKA, not Epac, is the predominant and physiologically relevant effector through which β-agonists exert their relaxant effects.
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