Abstract
The endocannabinoids anandamide and 2-arachidonoylglycerol are lipid mediators that signal via CB1 and CB2 cannabinoid receptors and Gi/o-proteins to inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase. In the brain, CB1 receptors interact with opioid receptors in close proximity, and these receptors may share G-proteins and effector systems. In the striatum, CB1 receptors function in coordination with D1 and D2 dopamine receptors, and combined stimulation of CB1-D2 receptor heteromeric complexes promotes a unique interaction to stimulate cAMP production. CB1 receptors also trigger growth factor receptor signaling cascades in cells by engaging in cross-talk or interreceptor signal transmission with the receptor tyrosine kinase (RTK) family. Mechanisms for CB1 receptor-RTK transactivation can include stimulation of signal transduction pathways regulated by second messengers as well as phospholipase C, metalloprotease cleavage of membrane-bound precursor proteins such as epidermal growth factor which activate RTKs, RTK autophosphorylation, and recruitment of non-receptor tyrosine kinases. CB1 and CB2 receptors are expressed in peripheral tissues including liver and adipose tissue, and are induced in pathological conditions. Novel signal transduction resulting from endocannabinoid regulation of AMP-regulated kinase and peroxisome proliferator-activated receptors have been discovered from studies of hepatocytes and adipocytes. It can be predicted that drug discovery of the future will be based upon these novel signal transduction mechanisms for endocannabinoid mediators.
Keywords: Anandamide, 2-arachidonoylglycerol, cannabinoid receptor heteromers, endocannabinoid, extracellular signalregulated kinase, G-proteins, receptor tyrosine kinases, peroxisome proliferator-activated receptor
CNS & Neurological Disorders - Drug Targets
Title: Signal Transduction via Cannabinoid Receptors
Volume: 8 Issue: 6
Author(s): George D. Dalton, Caroline E. Bass, Cynthia G. Van Horn and Allyn C. Howlett
Affiliation:
Keywords: Anandamide, 2-arachidonoylglycerol, cannabinoid receptor heteromers, endocannabinoid, extracellular signalregulated kinase, G-proteins, receptor tyrosine kinases, peroxisome proliferator-activated receptor
Abstract: The endocannabinoids anandamide and 2-arachidonoylglycerol are lipid mediators that signal via CB1 and CB2 cannabinoid receptors and Gi/o-proteins to inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase. In the brain, CB1 receptors interact with opioid receptors in close proximity, and these receptors may share G-proteins and effector systems. In the striatum, CB1 receptors function in coordination with D1 and D2 dopamine receptors, and combined stimulation of CB1-D2 receptor heteromeric complexes promotes a unique interaction to stimulate cAMP production. CB1 receptors also trigger growth factor receptor signaling cascades in cells by engaging in cross-talk or interreceptor signal transmission with the receptor tyrosine kinase (RTK) family. Mechanisms for CB1 receptor-RTK transactivation can include stimulation of signal transduction pathways regulated by second messengers as well as phospholipase C, metalloprotease cleavage of membrane-bound precursor proteins such as epidermal growth factor which activate RTKs, RTK autophosphorylation, and recruitment of non-receptor tyrosine kinases. CB1 and CB2 receptors are expressed in peripheral tissues including liver and adipose tissue, and are induced in pathological conditions. Novel signal transduction resulting from endocannabinoid regulation of AMP-regulated kinase and peroxisome proliferator-activated receptors have been discovered from studies of hepatocytes and adipocytes. It can be predicted that drug discovery of the future will be based upon these novel signal transduction mechanisms for endocannabinoid mediators.
Export Options
About this article
Cite this article as:
Dalton D. George, Bass E. Caroline, Van Horn G. Cynthia and Howlett C. Allyn, Signal Transduction via Cannabinoid Receptors, CNS & Neurological Disorders - Drug Targets 2009; 8 (6) . https://dx.doi.org/10.2174/187152709789824615
DOI https://dx.doi.org/10.2174/187152709789824615 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
The Neurotachykinin NK1 Receptor – A Novel Target for Diagnostics and Therapy
Current Molecular Imaging (Discontinued) Therapeutic Approaches to Modulating Glutathione Levels as a Pharmacological Strategy in Alzheimer`s Disease
Current Alzheimer Research Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer’s Disease Patients?
CNS & Neurological Disorders - Drug Targets Mechanisms Involved in BACE Upregulation Associated to Stress
Current Alzheimer Research The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review
Current Genomics A Combination of Two Antioxidants (An SOD Mimic and Ascorbate) Produces a Pro-Oxidative Effect Forcing Escherichia coli to Adapt Via Induction of oxyR Regulon
Anti-Cancer Agents in Medicinal Chemistry Gene and Cancer Therapy - Pseudorabies Virus: A Novel Research and Therapeutic Tool?
Current Gene Therapy Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases
Current Medicinal Chemistry The High Throughput Biomedicine Unit at the Institute for Molecular Medicine Finland: High Throughput Screening Meets Precision Medicine
Combinatorial Chemistry & High Throughput Screening Effects of Vitamin A Deficiency and Opioids on Parvalbumin + Interneurons in the Hippocampus of the HIV-1 Transgenic Rat
Current HIV Research Mitochondrial Superoxide Dismutase: A Promising Target for New Anticancer Therapies
Current Medicinal Chemistry Biocompatibility and Neuroprotective Potential of Encapsulated S-Allyl-L-Cysteine into PCL-based Nanocarrier
Drug Delivery Letters Elucidation of Abnormal Extracellular Regulated Kinase (ERK) Signaling and Associations with Syndromic and Non-syndromic Autism
Current Drug Targets Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008
Anti-Cancer Agents in Medicinal Chemistry Diabetes Mellitus: Channeling Care through Cellular Discovery
Current Neurovascular Research Targeting the Pleiotrophin/Receptor Protein Tyrosine Phosphatase β /ζ Signaling Pathway to Limit Neurotoxicity Induced by Drug Abuse
Mini-Reviews in Medicinal Chemistry Lipid Modulation of Intravascular and Cellular Sodium Handling:Mechanistic Insights and Potential Clinical Implications
Current Vascular Pharmacology Solid Phase Synthesis of Oxytocin Analogues Conjugated to Polyamino Polycarboxylic Ligands
Letters in Organic Chemistry Melittin: A Natural Peptide with Expanded Therapeutic Applications
The Natural Products Journal