ArticleProceedings of the National Academy of Sciences of the United States of America2009
Identification of intracellular carriers for the endocannabinoid anandamide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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Who cites it
191 citing papers in PubMed, 361 citations in OpenAlex.
- FABP5 deletion in nociceptors augments endocannabinoid signaling and suppresses TRPV1 sensitization and inflammatory pain.Scientific reports · 2022Trial
- Sterol carrier protein 2 loss reduces anxiety and enhances fear extinction.Journal of affective disorders · 2026Article
- Fatty Acid-Binding Proteins and Substance Use Disorders: From Lipid Signaling to Therapeutic Targets.Genes · 2026Review
- Docosahexaenoic Acid Protects Schwann Cells Against Palmitic Acid-Induced Lipotoxicity by Modulating Autophagy, ER Stress, and Lipid Handling.Neurochemical research · 2026Article
- Acute Pain After Total Knee Arthroplasty: 2-Arachidonoylglycerol Tone and Endocannabinoid/Eicosanoid Crosstalk.Anesthesia and analgesia · 2026Article
- Cannabinoids in immune system-related diseases: From bench to clinic.Chinese medical journal · 2026Review
- Integrative network analysis reveals organizational principles of the endocannabinoid system.Journal of cannabis research · 2026Article
- Evaluating FABP5 as a Therapeutic Target for Pain Management.European journal of pain (London, England) · 2026Review
- Serotonergic Signaling Rewired: A Lipid Raft-Controlled Model of Synaptic Transmission Grounded in the Fundamental Parameters of Biological Systems.Life (Basel, Switzerland) · 2026Article
- Chemical Probes for Investigating the Endocannabinoid System.Current topics in behavioral neurosciences · 2026Review
- Cannabinoid-based Pharmacology for the Management of Substance Use Disorders.Current topics in behavioral neurosciences · 2026Review
- FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Circuit mechanisms governing endocannabinoid modulation of affective behaviour and stress adaptation.Nature reviews. Neuroscience · 2025Review
- Interaction of sortilin with apolipoprotein E3 enables neurons to use long-chain fatty acids as alternative metabolic fuel.Nature metabolism · 2025Article
- Topical β-Caryophyllene for Dermatologic Disorders: Mechanisms, Human Evidence, and Clinical Translation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A Neural-Glial Model of the ApoE-SORT1-FABP7 Axis Tied to Sleep Disruption and Alzheimer's Disease Pathophysiology.Biomolecules · 2025Review
- The influence of genetics on the endocannabinoid system gene expression and relevance for targeting reproductive conditions.Journal of cannabis research · 2025Article
- Article
- The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ART26.12, a novel fatty acid-binding protein 5 inhibitor, shows efficacy in multiple preclinical neuropathy models.European journal of pain (London, England) · 2025Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) is an uncharged neuromodulatory lipid that, similar to many neurotransmitters, is inactivated through its cellular uptake and subsequent catabolism. AEA is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum. In contrast to most neuromodulators, the hydrophilic cytosol poses a diffusional barrier for the efficient delivery of AEA to its site of catabolism. Therefore, AEA likely traverses the cytosol with the assistance of an intracellular carrier that increases its solubility and rate of diffusion. To study this process, AEA uptake and hydrolysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondria, or the Golgi apparatus. AEA hydrolysis was detectable at the earliest measurable time point (3 seconds), suggesting that COS-7 cells, normally devoid of an endocannabinoid system, possess an efficient cytosolic trafficking mechanism for AEA. Three fatty acid binding proteins (FABPs) known to be expressed in brain were examined as possible intracellular AEA carriers. AEA uptake and hydrolysis were significantly potentiated in N18TG2 neuroblastoma cells after overexpression of FABP5 or FABP7, but not FABP3. Similar results were observed in COS-7 cells stably expressing FAAH. Consistent with the roles of FABP as AEA carriers, administration of the competitive FABP ligand oleic acid or the selective non-lipid FABP inhibitor BMS309403 attenuated AEA uptake and hydrolysis by approximately 50% in N18TG2 and COS-7 cells. Taken together, FABPs represent the first proteins known to transport AEA from the plasma membrane to FAAH for inactivation and may therefore be novel pharmacological targets.
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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.