ArticleThe Journal of physiology2007
A critical role of the cAMP sensor Epac in switching protein kinase signalling in prostaglandin E2-induced potentiation of P2X3 receptor currents in inflamed rats.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Exercise, Prostaglandin ECells · 2026Review
- Inhibition of EPAC1 Prevents Neuronal Death Mediated by Diesel Exhaust Particles in Ferroptotic Cell Death Conditions.Antioxidants (Basel, Switzerland) · 2026Article
- Role of EPAC1 in chronic pain.Biochemistry and biophysics reports · 2024Review
- Pyruvate Upregulates Hepatic FGF21 Expression by Activating PDE and Inhibiting cAMP-Epac-CREB Signaling Pathway.International journal of molecular sciences · 2022Article
- Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation of Mitochondrial Function by Epac2 Contributes to Acute Inflammatory Hyperalgesia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and CaReviews of physiology, biochemistry and pharmacology · 2021Review
- P2X3 receptors contribute to transition from acute to chronic muscle pain.Purinergic signalling · 2020Article
- Molecular mechanisms underlying the actions of arachidonic acid-derived prostaglandins on peripheral nociception.Journal of neuroinflammation · 2020Review
- Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia.British journal of pharmacology · 2018Article
- Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- CBNeurochemical research · 2018Article
- Electroacupuncture Attenuates Induction of Inflammatory Pain by Regulating Opioid and Adenosine Pathways in Mice.Scientific reports · 2017Article
- Article
- Epac1 interacts with importin β1 and controls neurite outgrowth independently of cAMP and Rap1.Scientific reports · 2016Article
- Long-term exposure to PGE2 causes homologous desensitization of receptor-mediated activation of protein kinase A.Journal of neuroinflammation · 2016Article
- Epac-protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation.Pain · 2016Article
- Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- P2X ion channel receptors and inflammation.Purinergic signalling · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sensitization of purinergic P2X receptors is one of the mechanisms responsible for exaggerated pain responses to inflammatory injuries. Prostaglandin E2 (PGE2), produced by inflamed tissues, is known to contribute to abnormal pain states. In a previous study, we showed that PGE2 increases fast inactivating ATP currents that are mediated by homomeric P2X3 receptors in dorsal root ganglion (DRG) neurons isolated from normal rats. Protein kinase A (PKA) is the signalling pathway used by PGE2. Little is known about the action of PGE2 on ATP currents after inflammation, although the information is crucial for understanding the mechanisms underlying inflammation-induced sensitization of P2X receptors. We therefore studied the effects of PGE2 on P2X3 receptor-mediated ATP currents in DRG neurons dissociated from complete Freund's adjuvant (CFA)-induced inflamed rats. We found that PGE2 produces a large increase in ATP currents. PKCepsilon, in addition to PKA, becomes involved in the modulatory action of PGE2. Thus, PGE2 signalling switches from a solely PKA-dependent pathway under normal conditions to both PKA- and PKC-dependent pathways after inflammation. Studying the mechanisms underlying the switch, we demonstrated that cAMP-responsive guanine nucleotide exchange factor 1 (Epac1) is up-regulated after inflammation. The Epac agonist CPT-OMe mimics the potentiating effect of PGE2 and occludes the PKC-mediated PGE2 action on ATP currents. These results suggest that Epac plays a critical role in P2X3 sensitization by activation of de novo PKC-dependent signalling of PGE2 after inflammation and would be a useful therapeutic target for pain therapies.
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