ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2002
PKA/AKAP/VR-1 module: A common link of Gs-mediated signaling to thermal hyperalgesia.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed.
- An update on regulation of the polymodal TRPV4 channel by protein phosphorylation.Channels (Austin, Tex.) · 2026Review
- Enhanced TRPV1 activation through TLR-4 and PKA signaling in Dorsal Root Ganglia Neurons.bioRxiv : the preprint server for biology · 2026Article
- Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The dual role of TRPV1 in peripheral neuropathic pain: pain switches caused by its sensitization or desensitization.Frontiers in molecular neuroscience · 2024Review
- Exaptation and Evolutionary Adaptation in Nociceptor Mechanisms Driving Persistent Pain.Brain, behavior and evolution · 2023Review
- Transient Receptor Potential Vanilloid 1 Signaling Is Independent on Protein Kinase A Phosphorylation of Ankyrin-Rich Membrane Spanning Protein.Medical sciences (Basel, Switzerland) · 2022Article
- Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1.European journal of pain (London, England) · 2022Article
- Protein kinase C-mediated phosphorylation of transient receptor potential melastatin type 2 Thr738 counteracts the effect of cytosolic CaThe Journal of physiology · 2022Article
- Nociceptive signaling through transient receptor potential vanilloid 1 is regulated by Cyclin Dependent Kinase 5-mediated phosphorylation of T407 in vivo.Molecular pain · 2022Article
- Oral cancer induced TRPV1 sensitization is mediated by PARScientific reports · 2022Article
- A review of non-prostanoid, eicosanoid receptors: expression, characterization, regulation, and mechanism of action.Journal of cell communication and signaling · 2022Review
- Inferiority complex: why do sensory ion channels multimerize?Biochemical Society transactions · 2022Review
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Depolarization induces nociceptor sensitization by CaV1.2-mediated PKA-II activation.The Journal of cell biology · 2021Article
- TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons.Scientific reports · 2021Article
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- Novel Analgesics with Peripheral Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Polymodal Activation and Desensitization of TRPV1 Receptor in Human Odontoblasts-Like Cells with Eugenol.International journal of dentistry · 2020Article
- Phosphorylation of TRPV1 S801 Contributes to Modality-Specific Hyperalgesia in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Modulation of osmotic stress-induced TRPV1 expression rescues human iPSC-derived retinal ganglion cells through PKA.Stem cell research & therapy · 2019Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory mediators not only activate "pain-"sensing neurons, the nociceptors, to trigger acute pain sensations, more important, they increase nociceptor responsiveness to produce inflammatory hyperalgesia. For example, prostaglandins activate G(s)-protein-coupled receptors and initiate cAMP- and protein kinase A (PKA)-mediated processes. We demonstrate for the first time at the cellular level that heat-activated ionic currents were potentiated after exposure to the cAMP activator forskolin in rat nociceptive neurons. The potentiation was prevented in the presence of the selective PKA inhibitor PKI(14-22), suggesting PKA-mediated phosphorylation of the heat transducer protein. PKA regulatory subunits were found in close vicinity to the plasma membrane in these neurons, and PKA catalytic subunits only translocated to the cell periphery when activated. The translocation and the current potentiation were abolished in the presence of an A-kinase anchoring protein (AKAP) inhibitor. Similar current changes after PKA activation were obtained from human embryonic kidney 293t cells transfected with the wild-type heat transducer protein vanilloid receptor 1 (VR-1). The forskolin-induced current potentiation was greatly reduced in cells transfected with VR-1 mutants carrying point mutations at the predicted PKA phosphorylation sites. The heat transducer VR-1 is therefore suggested as the molecular target of PKA phosphorylation, and potentiation of current responses to heat depends on phosphorylation at predicted PKA consensus sites. Thus, the PKA/AKAP/VR-1 module presents as the molecular correlate of G(s)-mediated inflammatory hyperalgesia.
Indexed as
Identifiers
12040081PMC6758778What OpenQuestion holds
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.