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 proNGF-p75NTR-Sortilin Signalling Complex as New Target for the Therapeutic Treatment of Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Antiproliferative Effects of Molecular Iodine in Cancers
Current Chemical Biology Interaction Between Estrogen Receptor Alpha and Insulin/IGF Signaling in Breast Cancer
Current Cancer Drug Targets The Long Non-Coding RNAs in Neurodegenerative Diseases: Novel Mechanisms of Pathogenesis
Current Alzheimer Research Cyclin-Dependent Kinase Inhibitors as Anticancer Drugs
Current Drug Targets New Insights on the Antitumoral Properties of Prodiginines
Current Medicinal Chemistry Molecular Mechanisms of Pancreatic Cancer Dissemination: The Role of the Chemokine System
Current Pharmaceutical Design Neuroprotective Role of Natural Polyphenols
Current Topics in Medicinal Chemistry Relevance of Protein Isoforms in Proteomic Studies
Current Proteomics Imatinib Reduces the Vasculogenic Potential of Plastic Tumor Cells
Current Angiogenesis (Discontinued) Determination of Human Serum α1-Acid Glycoprotein and Albumin Binding of Various Marketed and Preclinical Kinase Inhibitors
Current Medicinal Chemistry An Effective HIV Vaccine: A Combination of Humoral and Cellular Immunity?
Current HIV Research STAT3 as a Therapeutic Target for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry New Perspective on the Dual Functions of Indirubins in Cancer Therapy and Neuroprotection
Anti-Cancer Agents in Medicinal Chemistry Drug Transporters and Multiple Drug Resistance in the Most Common Pediatric Solid Tumors
Current Drug Metabolism Phytoestrogens: Implications in Neurovascular Research
Current Neurovascular Research Mitochondria: A Promising Target for Anticancer Alkaloids
Current Topics in Medicinal Chemistry Down with the Erythropoietin. Long Live the Erythropoietin !
Current Drug Targets Inhibition of Apoptosis in Pediatric Cancer by Survivin
Current Pediatric Reviews Multimodality Imaging of CXCR4 in Cancer: Current Status towards Clinical Translation
Current Molecular Medicine