ArticleMolecular pharmacology2017
Ceramide 1-Phosphate Increases P-Glycoprotein Transport Activity at the Blood-Brain Barrier via Prostaglandin E2 Signaling.
Article in Molecular pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The trial behind it
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- A potential of serum anti-C1P IgG antibodies as biomarkers in differential diagnosis of relapsing-remitting multiple sclerosis.Scientific reports · 2026Article
- Ceramides and neuroinflammation as immunometabolic drivers and biomarkers of major depressive disorder, treatment-resistant depression, and suicidal vulnerability.Frontiers in pharmacology · 2026Review
- Presence and relevance of serum anti-C1P IgG antibodies in relapsing-remitting multiple sclerosis.Research square · 2025Article
- Role of Ceramide Kinase/C1P in the Regulation of Cell Growth and Survival.International journal of molecular sciences · 2025Review
- Exploring novel roles of lipid droplets and lipid metabolism in regulating inflammation and blood-brain barrier function in neurological diseases.Frontiers in neuroscience · 2025Review
- ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery.Pharmacological reviews · 2023Review
- Dysregulated lipid metabolism in TMZ-resistant glioblastoma: pathways, proteins, metabolites and therapeutic opportunities.Lipids in health and disease · 2023Review
- Regulation of P-Glycoprotein in the Brain.International journal of molecular sciences · 2022Review
- Dysfunction of ABC Transporters at the Surface of BBB: Potential Implications in Intractable Epilepsy and Applications of Nanotechnology Enabled Drug Delivery.Current drug metabolism · 2022Review
- Evaluation of sphingolipid metabolism on diabetic retinopathy.Indian journal of ophthalmology · 2021Article
- A Comprehensive Analysis of Metabolomics and Transcriptomics Reveals Novel Biomarkers and Mechanistic Insights on Lorlatinib Crosses the Blood-Brain Barrier.Frontiers in pharmacology · 2021Article
- Distinctive sphingolipid patterns in chronic multiple sclerosis lesions.Journal of lipid research · 2020Article
- Clinical application of ceramide in cancer treatment.Breast cancer (Tokyo, Japan) · 2019Review
- Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Acute pain alters P-glycoprotein-containing protein complexes in rat cerebral microvessels: Implications for P-glycoprotein trafficking.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Isolation of Cerebral Capillaries from Fresh Human Brain Tissue.Journal of visualized experiments : JoVE · 2018Article
- A Simple and Reproducible Method to Prepare Membrane Samples from Freshly Isolated Rat Brain Microvessels.Journal of visualized experiments : JoVE · 2018Article
- Sphingolipid Metabolism: A New Therapeutic Opportunity for Brain Degenerative Disorders.Frontiers in neuroscience · 2018Review
- mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus.International journal of nanomedicine · 2017Article
- The Role of Sphingosine-1-Phosphate and Ceramide-1-Phosphate in Inflammation and Cancer.Mediators of inflammation · 2017Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
P-glycoprotein, an ATP-driven efflux pump, regulates permeability of the blood-brain barrier (BBB). Sphingolipids, endogenous to brain tissue, influence inflammatory responses and cell survival in vitro. Our laboratory has previously shown that sphingolipid signaling by sphingosine 1-phosphate decreases basal P-glycoprotein transport activity. Here, we investigated the potential for another sphingolipid, ceramide 1-phosphate (C1P), to modulate efflux pumps at the BBB. Using confocal microscopy and measuring luminal accumulation of fluorescent substrates, we assessed the transport activity of several efflux pumps in isolated rat brain capillaries. C1P treatment induced P-glycoprotein transport activity in brain capillaries rapidly and reversibly. In contrast, C1P did not affect transport activity of two other major efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein. C1P induced P-glycoprotein transport activity without changing transporter protein expression. Inhibition of the key signaling components in the cyclooxygenase-2 (COX-2)/prostaglandin E2 signaling cascade (phospholipase A2, COX-2, multidrug resistance protein 4, and G-protein-coupled prostaglandin E2 receptors 1 and 2), abolished P-glycoprotein induction by C1P. We show that COX-2 and prostaglandin E2 are required for C1P-mediated increases in P-glycoprotein activity independent of transporter protein expression. This work describes how C1P activates a signaling cascade to dynamically regulate P-glycoprotein transport at the BBB and offers potential clinical targets to modulate neuroprotection and drug delivery to the CNS.
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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.