ArticleThe Journal of clinical investigation2016
Phosphorylation state-dependent modulation of spinal glycine receptors alleviates inflammatory pain.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Mechanism of human α3β GlyR regulation by intracellular M3/M4 loop phosphorylation and 2,6-di-tert-butylphenol interaction.Nature communications · 2025Article
- Allosteric modulation and direct activation of glycine receptors by a tricyclic sulfonamide.Scientific reports · 2025Article
- Molecular investigation of ergot alkaloid ergotamine's modulatory effects on glycine receptors expressed inComputational and structural biotechnology journal · 2025Article
- Streptozotocin-Induced Diabetic Rats Showed a Differential Glycine Receptor Expression in the Spinal Cord: A GlyR Role in Diabetic Neuropathy.Neurochemical research · 2024Article
- Asymmetric gating of a human hetero-pentameric glycine receptor.Nature communications · 2023Article
- An anchor-tether 'hindered' HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.British journal of anaesthesia · 2023Article
- Loss of Extrasynaptic Inhibitory Glycine Receptors in the Hippocampus of an AD Mouse Model Is Restored by Treatment with Artesunate.International journal of molecular sciences · 2023Article
- Hetero-pentamerization determines mobility and conductance of Glycine receptor α3 splice variants.Cellular and molecular life sciences : CMLS · 2022Article
- Cannabidiol and substance use disorder: Dream or reality.Neuropharmacology · 2022Review
- Glycinergic Modulation of Pain in Behavioral Animal Models.Frontiers in pharmacology · 2022Review
- Glycine Receptor Subtypes and Their Roles in Nociception and Chronic Pain.Frontiers in molecular neuroscience · 2022Review
- Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor.Cellular and molecular life sciences : CMLS · 2021Article
- Glycine Receptors in Spinal Nociceptive Control-An Update.Biomolecules · 2021Review
- Analgesia for Sheep in Commercial Production: Where to Next?Animals : an open access journal from MDPI · 2021Review
- Modulation of Glycinergic Neurotransmission may Contribute to the Analgesic Effects of Propacetamol.Biomolecules · 2021Article
- Effects of Interleukin-1β in Glycinergic Transmission at the Central Amygdala.Frontiers in pharmacology · 2021Article
- Non-canonical Molecular Targets for Novel Analgesics: Intracellular Calcium and HCN Channels.Current neuropharmacology · 2021Review
- Modulation of glycine receptor single-channel conductance by intracellular phosphorylation.Scientific reports · 2020Article
- Inhibition of the Glycine Receptor alpha 3 Function by Colchicine.Frontiers in pharmacology · 2020Article
- Pentameric Ligand-Gated Ion Channels as Pharmacological Targets Against Chronic Pain.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Diminished inhibitory neurotransmission in the superficial dorsal horn of the spinal cord is thought to contribute to chronic pain. In inflammatory pain, reductions in synaptic inhibition occur partially through prostaglandin E2- (PGE2-) and PKA-dependent phosphorylation of a specific subtype of glycine receptors (GlyRs) that contain α3 subunits. Here, we demonstrated that 2,6-di-tert-butylphenol (2,6-DTBP), a nonanesthetic propofol derivative, reverses inflammation-mediated disinhibition through a specific interaction with heteromeric αβGlyRs containing phosphorylated α3 subunits. We expressed mutant GlyRs in HEK293T cells, and electrophysiological analyses of these receptors showed that 2,6-DTBP interacted with a conserved phenylalanine residue in the membrane-associated stretch between transmembrane regions 3 and 4 of the GlyR α3 subunit. In native murine spinal cord tissue, 2,6-DTBP modulated synaptic, presumably αβ heteromeric, GlyRs only after priming with PGE2. This observation is consistent with results obtained from molecular modeling of the α-β subunit interface and suggests that in α3βGlyRs, the binding site is accessible to 2,6-DTBP only after PKA-dependent phosphorylation. In murine models of inflammatory pain, 2,6-DTBP reduced inflammatory hyperalgesia in an α3GlyR-dependent manner. Together, our data thus establish that selective potentiation of GlyR function is a promising strategy against chronic inflammatory pain and that, to our knowledge, 2,6-DTBP has a unique pharmacological profile that favors an interaction with GlyRs that have been primed by peripheral inflammation.
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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.