Abstract
Adenosine A2A-dopamine D2 receptor interactions play a very important role in striatal function. A2A-D2 receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagonistic interactions between A2A and D2 receptors in the same neurons, the GABAergic enkephalinergic neurons. An antagonistic A2A-D2 intramembrane receptor interaction, which depends on A2A-D2 receptor heteromerization and Gq/11-PLC signaling, modulates neuronal excitability and neurotransmitter release. On the other hand, an antagonistic A2A-D2 receptor interaction at the adenylyl-cyclase level, which depends on Gs/olf- and Gi/o- type V adenylyl-cyclase signaling, modulates protein phosphorylation and gene expression. Finally, under conditions of upregulation of an activator of G protein signaling (AGS3), such as during chronic treatment with addictive drugs, a synergistic A2A-D2 receptor interaction can also be demonstrated. AGS3 facilitates a synergistic interaction between Gs/olf - and Gi/o-coupled receptors on the activation of types II/IV adenylyl cyclase, leading to a paradoxical increase in protein phosphorylation and gene expression upon co-activation of A2A and D2 receptors. The analysis of A2-D2 receptor interactions will have implications for the pathophysiology and treatment of basal ganglia disorders and drug addiction.
Keywords: Adenosine A2A Receptor, Dopamine D2 Receptor, G Protein-Coupled Receptors, Receptor Heteromers, Striatum, Basal Ganglia Disorders, Drug Addiction
Current Pharmaceutical Design
Title: An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors
Volume: 14 Issue: 15
Author(s): S. Ferre, C. Quiroz, A. S. Woods, R. Cunha, P. Popoli, F. Ciruela, C. Lluis, R. Franco, K. Azdad and S. N. Schiffmann
Affiliation:
Keywords: Adenosine A2A Receptor, Dopamine D2 Receptor, G Protein-Coupled Receptors, Receptor Heteromers, Striatum, Basal Ganglia Disorders, Drug Addiction
Abstract: Adenosine A2A-dopamine D2 receptor interactions play a very important role in striatal function. A2A-D2 receptor interactions provide an example of the capabilities of information processing by just two different G protein-coupled receptors. Thus, there is evidence for the coexistence of two reciprocal antagonistic interactions between A2A and D2 receptors in the same neurons, the GABAergic enkephalinergic neurons. An antagonistic A2A-D2 intramembrane receptor interaction, which depends on A2A-D2 receptor heteromerization and Gq/11-PLC signaling, modulates neuronal excitability and neurotransmitter release. On the other hand, an antagonistic A2A-D2 receptor interaction at the adenylyl-cyclase level, which depends on Gs/olf- and Gi/o- type V adenylyl-cyclase signaling, modulates protein phosphorylation and gene expression. Finally, under conditions of upregulation of an activator of G protein signaling (AGS3), such as during chronic treatment with addictive drugs, a synergistic A2A-D2 receptor interaction can also be demonstrated. AGS3 facilitates a synergistic interaction between Gs/olf - and Gi/o-coupled receptors on the activation of types II/IV adenylyl cyclase, leading to a paradoxical increase in protein phosphorylation and gene expression upon co-activation of A2A and D2 receptors. The analysis of A2-D2 receptor interactions will have implications for the pathophysiology and treatment of basal ganglia disorders and drug addiction.
Export Options
About this article
Cite this article as:
Ferre S., Quiroz C., Woods S. A., Cunha R., Popoli P., Ciruela F., Lluis C., Franco R., Azdad K. and Schiffmann N. S., An Update on Adenosine A2A-Dopamine D2 Receptor Interactions: Implications for the Function of G Protein-Coupled Receptors, Current Pharmaceutical Design 2008; 14 (15) . https://dx.doi.org/10.2174/138161208784480108
DOI https://dx.doi.org/10.2174/138161208784480108 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Getting Rid of Intracellular Aβ - Loss of Cellular Degradation Leads to Transfer Between Connected Neurons
Current Pharmaceutical Design Survival Signaling Pathways Activated by NMDA Receptors
Current Topics in Medicinal Chemistry Functional Biomarkers: an Approach to Bridge Pharmacokinetics and Pharmacodynamics in Pediatric Clinical Trials
Current Pharmaceutical Design The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders
Inflammation & Allergy - Drug Targets (Discontinued) Defining the Mechanism of Action of 4-Phenylbutyrate to Develop a Small-Molecule-Based Therapy for Alzheimers Disease
Current Medicinal Chemistry The Use of Therapeutic Peptides to Target and to Kill Cancer Cells
Current Medicinal Chemistry Targeting Parkinson’s - Tyrosine Hydroxylase and Oxidative Stress as Points of Interventions
CNS & Neurological Disorders - Drug Targets Regulation and Quantification of Cellular Mitochondrial Morphology and Content
Current Pharmaceutical Design Potential Control of Multiple Sclerosis by Cannabis and the Endocannabinoid System
CNS & Neurological Disorders - Drug Targets Electrochemical Study of Ellipticine Interaction with Single and Double Stranded Oligonucleotides
Anti-Cancer Agents in Medicinal Chemistry New Therapeutic Strategies for Cancer and Neurodegeneration Emerging from Yeast Cell-based Systems
Current Pharmaceutical Design Dendrimers as Novel Systems for Delivery of Neuropharmaceuticals to the Brain
CNS & Neurological Disorders - Drug Targets ROCK in CNS: Different Roles of Isoforms and Therapeutic Target for Neurodegenerative Disorders
Current Drug Targets Regulatory Triangle of Neurodegeneration, Adult Neurogenesis and MicroRNAs
CNS & Neurological Disorders - Drug Targets Methionine AminoPeptidase Type-2 Inhibitors Targeting Angiogenesis
Current Topics in Medicinal Chemistry Recent Advances and Approaches in Targeting Apoptosis Signaling Pathways for Anti-Cancer Therapeutics
Current Cancer Therapy Reviews Preparation, Characterization, and In Vitro Release of Vinorelbine Tartrate (VLBT)- Loaded Folate-conjugated Recombination Human Serum Albumin (rHSA) Nanoparticles with Different Degree of Cross-linking
Current Nanoscience CDC25A: A Rebel Within the CDC25 Phosphatases Family?
Anti-Cancer Agents in Medicinal Chemistry Developing Histone Deacetylase Inhibitors as Anti-Cancer Therapeutics
Current Medicinal Chemistry Fibroblast Growth Factor 2: From Laboratory Evidence to Clinical Application
Current Vascular Pharmacology