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
-
Ascorbic Acid: Its Role in Immune System and Chronic Inflammation Diseases
Mini-Reviews in Medicinal Chemistry Tumor Control by Manipulation of the Human Anti-Apoptotic Survivin Gene
Current Cancer Therapy Reviews Neglected Aspects of Drug Discovery - Microbiological Aspects
Current Clinical Pharmacology Modulation of Prion by Small Molecules: From Monovalent to Bivalent and Multivalent Ligands
Current Topics in Medicinal Chemistry Stress Hormone-Mediated DNA Damage Response -- Implications for Cellular Senescence and Tumour Progression
Current Drug Targets Emerging Potential of Naturally Occurring Autophagy Modulators Against Neurodegeneration
Current Pharmaceutical Design Calcium Ion – The Key Player in Cerebral Ischemia
Current Medicinal Chemistry Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy
Current Drug Targets Nongenomic Actions of Retinoids: Role of Nur77 and RXR in the Regulation of Apoptosis and Inflammation
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Isoindole Derivatives: Propitious Anticancer Structural Motifs
Current Topics in Medicinal Chemistry Peroxisome Proliferator Activated Receptor-Gamma Ligands as Potent Antineoplastic Agents
Current Medicinal Chemistry - Anti-Cancer Agents On Generating Uniform Bottom Shear Stress. Part II: Shear Stress Inducing Devices
Recent Patents on Chemical Engineering Do Pharmacological Approaches that Prevent Opioid Tolerance Target Different Elements in the Same Regulatory Machinery?
Current Drug Abuse Reviews Alteration of Ceramide 1-O-Functionalization as a Promising Approach for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Central Administration of Neuropeptide FF and Related Peptides Attenuate Systemic Morphine Analgesia in Mice
Protein & Peptide Letters Interactions of VDAC with Proteins Involved in Neurodegenerative Aggregation: An Opportunity for Advancement on Therapeutic Molecules
Current Medicinal Chemistry Sirtuin Modulators: Mechanisms and Potential Clinical Implications
Current Medicinal Chemistry Ganoderma lucidum: A Potential for Biotechnological Production of Anti-Cancer and Immunomodulatory Drugs
Recent Patents on Anti-Cancer Drug Discovery Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry New Adamantane Derivatives with Sigma Affinity and Antiproliferative Activity
Medicinal Chemistry