ArticleThe Journal of clinical investigation2006
Airway smooth muscle prostaglandin-EP1 receptors directly modulate beta2-adrenergic receptors within a unique heterodimeric complex.
Article in The Journal of clinical investigation, 2006. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed.
- Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.The Journal of allergy and clinical immunology · 2019Trial
- Persistent prostaglandin E2 upregulation and hormonal multi-resistance: A hypothesis for long COVID.Biochemistry and biophysics reports · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Orphan G protein-coupled receptor GPRC5B controls macrophage function by facilitating prostaglandin E receptor 2 signaling.Nature communications · 2025Article
- TAS2R5 screening reveals biased agonism that fails to evoke internalization and downregulation resulting in attenuated desensitization.PloS one · 2025Article
- A Review of Prostanoid Receptors: Expression, Characterization, Regulation, and Mechanism of Action.Journal of cell communication and signaling · 2021Review
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor.International journal of molecular sciences · 2020Review
- Signal Transduction and Pathogenic Modifications at the Melanocortin-4 Receptor: A Structural Perspective.Frontiers in endocrinology · 2019Article
- β2-Adrenergic Receptors Chaperone Trapped Bitter Taste Receptor 14 to the Cell Surface as a Heterodimer and Exert Unidirectional Desensitization of Taste Receptor Function.The Journal of biological chemistry · 2016Article
- Role of EP2 and EP4 receptors in airway microvascular leak induced by prostaglandin E2.British journal of pharmacology · 2016Article
- G Protein-Coupled Receptor Heteromers.Annual review of pharmacology and toxicology · 2016Review
- GPCR dimerization in brainstem nuclei contributes to the development of hypertension.British journal of pharmacology · 2015Article
- Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate vascular α₁-adrenergic receptor function.Molecular medicine (Cambridge, Mass.) · 2014Article
- Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2014Article
- Demonstration of a direct interaction between β2-adrenergic receptor and insulin receptor by BRET and bioinformatics.PloS one · 2014Article
- Bitter taste receptors on airway smooth muscle as targets for novel bronchodilators.Expert opinion on therapeutic targets · 2013Review
- Cross-desensitization and cointernalization of H1 and H2 histamine receptors reveal new insights into histamine signal integration.Molecular pharmacology · 2013Article
- cAMP regulation of airway smooth muscle function.Pulmonary pharmacology & therapeutics · 2013Review
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7 authors.
Funding
Abstract
Multiple and paradoxical effects of airway smooth muscle (ASM) 7-transmembrane-spanning receptors activated during asthma, or by treatment with bronchodilators such as beta(2)-adrenergic receptor (beta(2)AR) agonists, indicate extensive receptor crosstalk. We examined the signaling of the prostanoid-EP(1) receptor, since its endogenous agonist prostaglandin E(2) is abundant in the airway, but its functional implications are poorly defined. Activation of EP(1) failed to elicit ASM contraction in mouse trachea via this G(alphaq)-coupled receptor. However, EP(1) activation markedly reduced the bronchodilatory function of beta(2)AR agonist, but not forskolin, indicating an early pathway interaction. Activation of EP(1) reduced beta(2)AR-stimulated cAMP in ASM but did not promote or augment beta(2)AR phosphorylation or alter beta(2)AR trafficking. Bioluminescence resonant energy transfer showed EP(1) and beta(2)AR formed heterodimers, which were further modified by EP(1) agonist. In cell membrane [(35)S]GTPgammaS binding studies, the presence of the EP(1) component of the dimer uncoupled beta(2)AR from G(alphas), an effect accentuated by EP(1) agonist activation. Thus alone, EP(1) does not appear to have a significant direct effect on airway tone but acts as a modulator of the beta(2)AR, altering G(alphas) coupling via steric interactions imposed by the EP(1):beta(2)AR heterodimeric signaling complex and ultimately affecting beta(2)AR-mediated bronchial relaxation. This mechanism may contribute to beta-agonist resistance found in asthma.
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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.