Abstract
Endocannabinoids like anandamide and 2-arachidonoylglycerol bind and activate type-1 (CB1R) and type-2 (CB2R) cannabinoid receptors, two inhibitory G protein-coupled receptors (GPCRs) that are localized in the central nervous system and in peripheral tissues. The biological actions of these lipids are controlled through not yet fully characterized cellular mechanisms that regulate the release of endocannabinoids from membrane precursors, their uptake by cells, and their intracellular disposal. The transport of anadamide through the plasma membrane is saturable and energy-independent, and might occur through a putative anandamide membrane transporter. Altogether anandamide and 2-arachidonoylglycerol, their congeners and the proteins that bind, transport, synthesize and hydrolyze these lipids, form the “endocannabinoid system”. Accumulating evidence shows that CB1R (but not CB2R) binding and signaling, as well as anandamide transport, are under the control of lipid rafts (LRs), plasma membrane subdomains which modulate the activity of a number of GPCRs. Here we summarize the main features of the endocannabinoid system and LRs, in order to put the functional and structural effects of LRs on CB receptors, AEA transport and endocannabinoid signaling in a better focus. We outline the structural determinants that might explain the differential sensitivity of cannabic receptors towards raft integrity, and propose a general model to explain the dependence of endocannabinoid system on LRs. Finally, we also discuss the possible exploitation of LRs-targeted drugs as novel therapeutics for the treatment of endocannabinoid system-related pathologies.
Keywords: Cannabinoid receptors, caveolin, cholesterol, lipophilicity, membrane, signal transduction, transport, vanilloid receptor
Current Medicinal Chemistry
Title: Modulation of the Endocannabinoid System by Lipid Rafts
Volume: 14 Issue: 25
Author(s): Enrico Dainese, Sergio Oddi, Monica Bari and Mauro Maccarrone
Affiliation:
Keywords: Cannabinoid receptors, caveolin, cholesterol, lipophilicity, membrane, signal transduction, transport, vanilloid receptor
Abstract: Endocannabinoids like anandamide and 2-arachidonoylglycerol bind and activate type-1 (CB1R) and type-2 (CB2R) cannabinoid receptors, two inhibitory G protein-coupled receptors (GPCRs) that are localized in the central nervous system and in peripheral tissues. The biological actions of these lipids are controlled through not yet fully characterized cellular mechanisms that regulate the release of endocannabinoids from membrane precursors, their uptake by cells, and their intracellular disposal. The transport of anadamide through the plasma membrane is saturable and energy-independent, and might occur through a putative anandamide membrane transporter. Altogether anandamide and 2-arachidonoylglycerol, their congeners and the proteins that bind, transport, synthesize and hydrolyze these lipids, form the “endocannabinoid system”. Accumulating evidence shows that CB1R (but not CB2R) binding and signaling, as well as anandamide transport, are under the control of lipid rafts (LRs), plasma membrane subdomains which modulate the activity of a number of GPCRs. Here we summarize the main features of the endocannabinoid system and LRs, in order to put the functional and structural effects of LRs on CB receptors, AEA transport and endocannabinoid signaling in a better focus. We outline the structural determinants that might explain the differential sensitivity of cannabic receptors towards raft integrity, and propose a general model to explain the dependence of endocannabinoid system on LRs. Finally, we also discuss the possible exploitation of LRs-targeted drugs as novel therapeutics for the treatment of endocannabinoid system-related pathologies.
Export Options
About this article
Cite this article as:
Dainese Enrico, Oddi Sergio, Bari Monica and Maccarrone Mauro, Modulation of the Endocannabinoid System by Lipid Rafts, Current Medicinal Chemistry 2007; 14 (25) . https://dx.doi.org/10.2174/092986707782023235
DOI https://dx.doi.org/10.2174/092986707782023235 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Influence of Usnic Acid and its Derivatives on the Activity of Mammalian Poly(ADP-ribose)polymerase 1 and DNA Polymerase β
Medicinal Chemistry DNA Damage-inducing Compounds: Unraveling their Pleiotropic Effects Using High Throughput Sequencing
Current Medicinal Chemistry New Vessel Formation in the Central Nervous System During Tumor Growth, Vascular Malformations, and Moyamoya
Current Neurovascular Research Cellular Redox Modulator, ortho Mn(III) meso-tetrakis(N-n-Hexylpyridinium-2-yl)porphyrin, MnTnHex-2-PyP5+ in the Treatment of Brain Tumors
Anti-Cancer Agents in Medicinal Chemistry State of Art and Recent Developments of Anti-Cancer Strategies Based on TRAIL
Recent Patents on Anti-Cancer Drug Discovery Nanomedicine as a Strategy for Natural Compound Delivery to Prevent and Treat Cancers
Current Pharmaceutical Design The Immunoregulatory Protein Human B7H3 is a Tumor-Associated Antigen that Regulates Tumor Cell Migration and Invasion
Current Cancer Drug Targets β-Catenin/TCF-4 Signaling Regulates Susceptibility of Macrophages and Resistance of Monocytes to HIV-1 Productive Infection
Current HIV Research Specific Targeted Therapy: A New Tool for the Destruction of Cancer
Current Drug Therapy Therapeutic Window, a Critical Developmental Stage for Stem Cell Therapies
Current Stem Cell Research & Therapy Recent Advances in Liposomal Drug Delivery: A Review
Pharmaceutical Nanotechnology Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity
Current Medicinal Chemistry Nuclear Factor-κB: A Holy Grail in Cancer Prevention and Therapy
Current Signal Transduction Therapy Structural and Mechanistic Bases of the Anticancer Activity of Natural Aporphinoid Alkaloids
Current Topics in Medicinal Chemistry Novel Possible Pharmaceutical Research Tools: Stem Cells, Gene Delivery and their Combination
Current Pharmaceutical Design Chemistry of Tumour Targeted T1 Based MRI Contrast Agents
Current Topics in Medicinal Chemistry Targeted Nanosystems for Cancer Therapy
Current Cancer Therapy Reviews Presence of Intratumoral Stem Cells in Breast Cancer Patients with or without BRCA Germline Mutations
Current Cancer Drug Targets Multifunctional Anti-Cancer Nano-Platforms are Moving to Clinical Trials
Current Drug Metabolism Resveratrol, a Phytochemical Inducer of Multiple Cell Death Pathways: Apoptosis, Autophagy and Mitotic Catastrophe
Current Medicinal Chemistry