ArticlePloS one2013
Dissociations in the effects of β2-adrenergic receptor agonists on cAMP formation and superoxide production in human neutrophils: support for the concept of functional selectivity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Rap1A, Rap1B, and β-Adrenergic Signaling in Autologous HCT: A Randomized Controlled Trial of Propranolol.The Yale journal of biology and medicine · 2022Trial
- Crosstalk between circulating DPP3 and immune cells in the context of cardio-systemic stress.iScience · 2026Article
- Adrenergic effect on women's blood neutrophil oxidative activity the first day after delivery.JBRA assisted reproduction · 2024Article
- Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking.EMBO molecular medicine · 2023Article
- Adrenergic receptor signaling regulates the CD40-receptor mediated anti-tumor immunity.Frontiers in immunology · 2023Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- The role of βBrain, behavior, & immunity - health · 2021Article
- The stimulation and inhibition of beta-2 adrenergic receptor on the inflammatory responses of ovary and immune system in the aged laying hens.BMC veterinary research · 2021Article
- The role of neutrophils in neuro-immune modulation.Pharmacological research · 2020Review
- The Effect of βFrontiers in immunology · 2020Article
- α-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson's Disease Pathogenesis.Frontiers in neuroscience · 2018Review
- Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response.Frontiers in immunology · 2018Review
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- High constitutive Akt2 activity in U937 promonocytes: effective reduction of Akt2 phosphorylation by the histamine H2-receptor and the β2-adrenergic receptor.Naunyn-Schmiedeberg's archives of pharmacology · 2016Article
- Recruitment of β-arrestin 1 and 2 to the β2-adrenoceptor: analysis of 65 ligands.The Journal of pharmacology and experimental therapeutics · 2015Article
- Flow cytometric analysis with a fluorescently labeled formyl peptide receptor ligand as a new method to study the pharmacological profile of the histamine H2 receptor.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Adrenergic modulation of migration, CD11b and CD18 expression, ROS and interleukin-8 production by human polymorphonuclear leukocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015Article
- Adrenergic regulation of innate immunity: a review.Frontiers in pharmacology · 2015Review
- Structure-bias relationships for fenoterol stereoisomers in six molecular and cellular assays at the β2-adrenoceptor.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Divergent label-free cell phenotypic pharmacology of ligands at the overexpressed β₂-adrenergic receptors.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In neutrophils, activation of the β2-adrenergic receptor (β2AR), a Gs-coupled receptor, inhibits inflammatory responses, which could be therapeutically exploited. The aim of this study was to evaluate the effects of various β2AR ligands on adenosine-3',5'-cyclic monophosphate (cAMP) accumulation and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-induced superoxide anion (O2(•-)) production in human neutrophils and to probe the concept of ligand-specific receptor conformations (also referred to as functional selectivity or biased signaling) in a native cell system. This is an important question because so far, evidence for functional selectivity has been predominantly obtained with recombinant systems, due to the inherent difficulties to genetically manipulate human native cells. cAMP concentration was determined by HPLC/tandem mass spectrometry, and O2(•-) formation was assessed by superoxide dismutase-inhibitable reduction of ferricytochrome c. β2AR agonists were generally more potent in inhibiting fMLP-induced O2(•-) production than in stimulating cAMP accumulation. (-)-Ephedrine and dichloroisoproterenol were devoid of any agonistic activity in the cAMP assay, but partially inhibited fMLP-induced O2(•-) production. Moreover, (-)-adrenaline was equi-efficacious in both assays whereas the efficacy of salbutamol was more than two-fold higher in the O2(•-) assay. Functional selectivity was visualized by deviations of ligand potencies and efficacies from linear correlations for various parameters. We obtained no evidence for involvement of protein kinase A in the inhibition of fMLP-induced O2(•-) production after β2AR-stimulation although cAMP-increasing substances inhibited O2(•-) production. Taken together, our data corroborate the concept of ligand-specific receptor conformations with unique signaling capabilities in native human cells and suggest that the β2AR inhibits O2(•-) production in a cAMP-independent manner.
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