Abstract
Now there is general agreement that the purine nucleoside adenosine is an important neuromodulator in the central nervous system, playing a crucial role in neuronal excitability and synaptic/non-synaptic transmission in the hippocampus and basal ganglia. Adenosine is derived from the breakdown of extra- or intracellular ATP and is released upon a variety of physiological and pathological stimuli from neuronal and non-neuronal sources, i.e. from glial cells and exerts effects diffusing far away from release sites. The resultant elevation of adenosine levels in the extracellular space reaches micromolar level, and leads to the activation A1, A2A, A2B and A3 receptors, localized to pre- and postsynaptic as well as extrasynaptic sites. Activation of presynaptic A1 receptors inhibits the release of the majority of transmitters including glutamate, acetylcholine, noradrenaline, 5-HT and dopamine, whilst the stimulation of A2A receptors facilitates the release of glutamate and acetylcholine and inhibits the release of GABA. These actions underlie modulation of neuronal excitability, synaptic plasticity and coordination of neural networks and provide intriguing target sites for pharmacological intervention in ischemia and Parkinsons disease. However, despite that adenosine is also released during ischemia, A1 adenosine receptors do not participate in the modulation of excitotoxic glutamate release, which is nonsynaptic and is due to the reverse operation of transporters. Instead, extrasynaptic A1 receptors might be responsible for the neuroprotection afforded by A1 receptor activation.
Keywords: Adenosine, A1 receptor, A2A receptor, ATP, hippocampus, striatum, neuromodulator, GABA, neuronal excitability, excitotoxic glutamate release, neuroprotection, Ca2+-influx, ambient concentrations, Gi-coupled receptors
Current Topics in Medicinal Chemistry
Title: The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects
Volume: 11 Issue: 8
Author(s): Beata Sperlagh and E. Sylvester Vizi
Affiliation:
Keywords: Adenosine, A1 receptor, A2A receptor, ATP, hippocampus, striatum, neuromodulator, GABA, neuronal excitability, excitotoxic glutamate release, neuroprotection, Ca2+-influx, ambient concentrations, Gi-coupled receptors
Abstract: Now there is general agreement that the purine nucleoside adenosine is an important neuromodulator in the central nervous system, playing a crucial role in neuronal excitability and synaptic/non-synaptic transmission in the hippocampus and basal ganglia. Adenosine is derived from the breakdown of extra- or intracellular ATP and is released upon a variety of physiological and pathological stimuli from neuronal and non-neuronal sources, i.e. from glial cells and exerts effects diffusing far away from release sites. The resultant elevation of adenosine levels in the extracellular space reaches micromolar level, and leads to the activation A1, A2A, A2B and A3 receptors, localized to pre- and postsynaptic as well as extrasynaptic sites. Activation of presynaptic A1 receptors inhibits the release of the majority of transmitters including glutamate, acetylcholine, noradrenaline, 5-HT and dopamine, whilst the stimulation of A2A receptors facilitates the release of glutamate and acetylcholine and inhibits the release of GABA. These actions underlie modulation of neuronal excitability, synaptic plasticity and coordination of neural networks and provide intriguing target sites for pharmacological intervention in ischemia and Parkinsons disease. However, despite that adenosine is also released during ischemia, A1 adenosine receptors do not participate in the modulation of excitotoxic glutamate release, which is nonsynaptic and is due to the reverse operation of transporters. Instead, extrasynaptic A1 receptors might be responsible for the neuroprotection afforded by A1 receptor activation.
Export Options
About this article
Cite this article as:
Sperlagh Beata and Sylvester Vizi E., The Role of Extracellular Adenosine in Chemical Neurotransmission in the Hippocampus and Basal Ganglia: Pharmacological and Clinical Aspects, Current Topics in Medicinal Chemistry 2011; 11 (8) . https://dx.doi.org/10.2174/156802611795347564
DOI https://dx.doi.org/10.2174/156802611795347564 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Global Warming Favors Pathogenicity of the Brain-Eating Amoebae
Anti-Infective Agents Immunotherapy in a Natural Model of Aβ Pathogenesis: The Aging Beagle
CNS & Neurological Disorders - Drug Targets Novel Therapeutic Approaches to Autoimmune Demyelinating Disorders
Current Pharmaceutical Design Synthetic and Natural Immunomodulators Acting as Interferon Inducers
Current Pharmaceutical Design Small Ruminant Lentiviruses and Human Immunodeficiency Virus: Cousins that Take a Long View
Current HIV Research Catatonia: A Brief Update
Current Psychiatry Reviews The Utilization of Gene Targeting Models During in Preclinical Study of Drug Discovery Process - Example of Phenotypic and Functional Analysis of Cacna1 βGene Product
Current Pharmaceutical Biotechnology AMPA Receptor Antagonists: Potential Therapeutic Applications
Recent Patents on CNS Drug Discovery (Discontinued) Plant and Animal Steroids a New Hope to Search for Antiviral Agents
Current Medicinal Chemistry The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders
Inflammation & Allergy - Drug Targets (Discontinued) Etiology of Neuroinflammatory Pathologies in Neurodegenerative Diseases: A Treatise
Current Psychopharmacology Patent Selections
Recent Patents on Anti-Cancer Drug Discovery Possible Impact of Microglial Cells and the Monocyte-Macrophage System on Suicidal Behavior
CNS & Neurological Disorders - Drug Targets Drug Therapy of Neuropathic Pain: Current Developments and Future Perspectives
Current Drug Targets Liver X Receptor: Crosstalk Node for the Signaling of Lipid Metabolism,Carbohydrate Metabolism, and Innate Immunity
Current Signal Transduction Therapy Biological Activities of Yarrow Species (Achillea spp.)
Current Pharmaceutical Design Optic Neuritis: A Model for the Immuno-pathogenesis of Central Nervous System Inflammatory Demyelinating Diseases
Current Immunology Reviews (Discontinued) Nanomedicine in Therapeutic Intervention of Tuberculosis Meningitis
Current Nanoscience Conformational Hotspots of Dengue Virus NS5 RdRp
Current Bioinformatics Biochemistry and Biology of 2'-Fluoro-2'-Deoxythymidine (FT), A Putative Highly Selective Substrate for Thymidine Kinase Type 2 (TK2)
Current Radiopharmaceuticals