ArticleJournal of neuroinflammation2015
Sphingosine 1-phosphate enhances the excitability of rat sensory neurons through activation of sphingosine 1-phosphate receptors 1 and/or 3.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.Clinical pharmacology and therapeutics · 2020Pooled it
- Characterizing features of the genetic architecture underlying autism from a multi-ancestry perspective.Molecular psychiatry · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Fingolimod Effects on Motor Function and BDNF-TrkB Signaling in a Huntington's Mouse Model Are Disease-Stage-Dependent.International journal of molecular sciences · 2026Article
- The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.Epilepsia open · 2025Review
- Dissociation between the anti-allodynic effects of fingolimod (FTY720) and desensitization of S1PNeuropharmacology · 2024Article
- Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.BMC medicine · 2024Article
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- A novel co-target of ACY1 governing plasma membrane translocation of SphK1 contributes to inflammatory and neuropathic pain.iScience · 2023Article
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Liver's influence on the brain through the action of bile acids.Frontiers in neuroscience · 2023Review
- Inhibiting Sphingosine 1-Phosphate Receptor Subtype 3 Attenuates Brain Damage During Ischemia-Reperfusion Injury by Regulating nNOS/NO and Oxidative Stress.Frontiers in neuroscience · 2022Article
- Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses.International journal of molecular sciences · 2021Review
- Critical roles of sphingosine kinase 1 in the regulation of neuroinflammation and neuronal injury after spinal cord injury.Journal of neuroinflammation · 2021Article
- Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics.Trends in pharmacological sciences · 2020Review
- Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- Non-negligible factors in studying the ApoM-S1P axis using EA.hy926 cells.Annals of translational medicine · 2020Article
- Chloride - The Underrated Ion in Nociceptors.Frontiers in neuroscience · 2020Review
- O-cyclic phytosphingosine-1-phosphate stimulates HIF1α-dependent glycolytic reprogramming to enhance the therapeutic potential of mesenchymal stem cells.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts through a family of five G-protein-coupled receptors (S1PR1-5) and plays a key role in regulating the inflammatory response. Our previous studies demonstrated that rat sensory neurons express the mRNAs for all five S1PRs and that S1P increases neuronal excitability primarily, but not exclusively, through S1PR1. This raises the question as to which other S1PRs mediate the enhanced excitability.
methodsIsolated sensory neurons were treated with either short-interfering RNAs (siRNAs) or a variety of pharmacological agents targeted to S1PR1/R2/R3 to determine the role(s) of these receptors in regulating neuronal excitability. The excitability of isolated sensory neurons was assessed by using whole-cell patch-clamp recording to measure the capacity of these cells to fire action potentials (APs).
resultsAfter siRNA treatment, exposure to S1P failed to augment the excitability. Pooled siRNA targeted to S1PR1 and R3 also blocked the enhanced excitability produced by S1P. Consistent with the siRNA results, pretreatment with W146 and CAY10444, selective antagonists for S1PR1 and S1PR3, respectively, prevented the S1P-induced increase in neuronal excitability. Similarly, S1P failed to augment excitability after pretreatment with either VPC 23019, which is a S1PR1 and R3 antagonist, or VPC 44116, the phosphonate analog of VPC 23019. Acute exposure (10 to 15 min) to either of the well-established functional antagonists, FTY720 or CYM-5442, produced a significant increase in the excitability. Moreover, after a 1-h pretreatment with FTY720 (an agonist for S1PR1/R3/R4/R5), neither SEW2871 (S1PR1 selective agonist) nor S1P augmented the excitability. However, after pretreatment with CYM-5442 (selective for S1PR1), SEW2871 was ineffective, but S1P increased the excitability of some, but not all, sensory neurons.
conclusionsThese results demonstrate that the enhanced excitability produced by S1P is mediated by activation of S1PR1 and/or S1PR3.
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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.