ArticleThe Journal of experimental medicine2005
Calcium-sensing soluble adenylyl cyclase mediates TNF signal transduction in human neutrophils.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 68 citations in OpenAlex.
- Hyperammonemia increases the release of pathological extracellular vesicles from monocytes by impairing lysosomal function and autophagy through the TNFα-cAMP-PKA-LC3 pathway.Frontiers in immunology · 2025Article
- Albumin Nanoparticle Endocytosing Subset of Neutrophils for Precision Therapeutic Targeting of Inflammatory Tissue Injury.ACS nano · 2022Article
- Ion Channels, Transporters, and Sensors Interact with the Acidic Tumor Microenvironment to Modify Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2022Review
- Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase.Interface focus · 2021Review
- Molecular and biochemical characterization of the bicarbonate-sensing soluble adenylyl cyclase from a bony fish, the rainbow troutInterface focus · 2021Article
- Acetate attenuates inflammasome activation through GPR43-mediated CaExperimental & molecular medicine · 2019Article
- Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments.Journal of cardiovascular development and disease · 2018Review
- The Emerging Role of Soluble Adenylyl Cyclase in Primary Biliary Cholangitis.Digestive diseases (Basel, Switzerland) · 2017Review
- The Neutrophil Response Induced by an Agonist for Free Fatty Acid Receptor 2 (GPR43) Is Primed by Tumor Necrosis Factor Alpha and by Receptor Uncoupling from the Cytoskeleton but Attenuated by Tissue Recruitment.Molecular and cellular biology · 2016Article
- Soluble Adenylyl Cyclase Is Required for Retinal Ganglion Cell and Photoreceptor Differentiation.Investigative ophthalmology & visual science · 2016Article
- Different cAMP sources are critically involved in G protein-coupled receptor CRHR1 signaling.The Journal of cell biology · 2016Article
- Gαi2 and Gαi3 Differentially Regulate Arrest from Flow and Chemotaxis in Mouse Neutrophils.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Targeting G protein coupled receptor-related pathways as emerging molecular therapies.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2015Review
- The role of soluble adenylyl cyclase in neurite outgrowth.Biochimica et biophysica acta · 2014Review
- Central role of soluble adenylyl cyclase and cAMP in sperm physiology.Biochimica et biophysica acta · 2014Review
- pH sensing via bicarbonate-regulated "soluble" adenylyl cyclase (sAC).Frontiers in physiology · 2013Review
- Multiple facets of cAMP signalling and physiological impact: cAMP compartmentalization in the lung.Pharmaceuticals (Basel, Switzerland) · 2012Article
- Soluble adenylyl cyclase activity is necessary for retinal ganglion cell survival and axon growth.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- Activation of soluble adenylyl cyclase protects against secretagogue stimulated zymogen activation in rat pancreaic acinar cells.PloS one · 2012Article
- Lipoic acid stimulates cAMP production via G protein-coupled receptor-dependent and -independent mechanisms.The Journal of nutritional biochemistry · 2011Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Through chemical screening, we identified a pyrazolone that reversibly blocked the activation of phagocyte oxidase (phox) in human neutrophils in response to tumor necrosis factor (TNF) or formylated peptide. The pyrazolone spared activation of phox by phorbol ester or bacteria, bacterial killing, TNF-induced granule exocytosis and phox assembly, and endothelial transmigration. We traced the pyrazolone's mechanism of action to inhibition of TNF-induced intracellular Ca2+ elevations, and identified a nontransmembrane ("soluble") adenylyl cyclase (sAC) in neutrophils as a Ca2+-sensing source of cAMP. A sAC inhibitor mimicked the pyrazolone's effect on phox. Both compounds blocked TNF-induced activation of Rap1A, a phox-associated guanosine triphosphatase that is regulated by cAMP. Thus, TNF turns on phox through a Ca2+-triggered, sAC-dependent process that may involve activation of Rap1A. This pathway may offer opportunities to suppress oxidative damage during inflammation without blocking antimicrobial function.
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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.