Abstract
This paper presents an overview of the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the central nervous system, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. The endogenous somnogen prostaglandin (PG) D2 increases the extracellular level of adenosine under the subarachnoid space of the basal forebrain and promotes physiological sleep. Adenosine is neither stored nor released as a classical neurotransmitter and is thought to be formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The extracellular concentration of adenosine increases in the cortex and basal forebrain during prolonged wakefulness and decreases during the sleep recovery period. Therefore, adenosine is proposed to act as a homeostatic regulator of sleep and to be a link between the humoral and neural mechanisms of sleep-wake regulation. Both the adenosine A1 receptor (A1R) and A2AR are involved in sleep induction. The A2AR plays a predominant role in the somnogenic effects of PGD2. By use of genemanipulated mice, the arousal effect of caffeine was shown to be dependent on the A2AR. On the other hand, inhibition of wake-promoting neurons via the A1R also mediates the sleep-inducing effects of adenosine, whereas activation of A1R in the lateral preoptic area induces wakefulness, suggesting that A1R regulates the sleep-wake cycle in a site-dependent manner. The potential therapeutic applications of agonists and antagonists of these receptors in sleep disorders are briefly discussed.
Keywords: Adenosine, knockout mice, prostaglandin D2, receptor, sleep, wakefulness, sleep-wake regulation, endogenous somnogen prostaglandin, cortex, homeostatic regulator of sleep, somnogenic effects, genemanipulated mice, caffeine, wake-promoting neurons, sleep-wake cycle
Current Topics in Medicinal Chemistry
Title: The Role of Adenosine in the Regulation of Sleep
Volume: 11 Issue: 8
Author(s): Zhi-Li Huang, Yoshihiro Urade and Osamu Hayaishi
Affiliation:
Keywords: Adenosine, knockout mice, prostaglandin D2, receptor, sleep, wakefulness, sleep-wake regulation, endogenous somnogen prostaglandin, cortex, homeostatic regulator of sleep, somnogenic effects, genemanipulated mice, caffeine, wake-promoting neurons, sleep-wake cycle
Abstract: This paper presents an overview of the current knowledge about the role of adenosine in the sleep-wake regulation with a focus on adenosine in the central nervous system, regulation of adenosine levels, adenosine receptors, and manipulations of the adenosine system by the use of pharmacological and molecular biological tools. The endogenous somnogen prostaglandin (PG) D2 increases the extracellular level of adenosine under the subarachnoid space of the basal forebrain and promotes physiological sleep. Adenosine is neither stored nor released as a classical neurotransmitter and is thought to be formed inside cells or on their surface, mostly by breakdown of adenine nucleotides. The extracellular concentration of adenosine increases in the cortex and basal forebrain during prolonged wakefulness and decreases during the sleep recovery period. Therefore, adenosine is proposed to act as a homeostatic regulator of sleep and to be a link between the humoral and neural mechanisms of sleep-wake regulation. Both the adenosine A1 receptor (A1R) and A2AR are involved in sleep induction. The A2AR plays a predominant role in the somnogenic effects of PGD2. By use of genemanipulated mice, the arousal effect of caffeine was shown to be dependent on the A2AR. On the other hand, inhibition of wake-promoting neurons via the A1R also mediates the sleep-inducing effects of adenosine, whereas activation of A1R in the lateral preoptic area induces wakefulness, suggesting that A1R regulates the sleep-wake cycle in a site-dependent manner. The potential therapeutic applications of agonists and antagonists of these receptors in sleep disorders are briefly discussed.
Export Options
About this article
Cite this article as:
Huang Zhi-Li, Urade Yoshihiro and Hayaishi Osamu, The Role of Adenosine in the Regulation of Sleep, Current Topics in Medicinal Chemistry 2011; 11 (8) . https://dx.doi.org/10.2174/156802611795347654
DOI https://dx.doi.org/10.2174/156802611795347654 |
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
-
Nanotech Revolution for the Anti-Cancer Drug Delivery through Blood- Brain-Barrier
Current Cancer Drug Targets Therapeutic Nucleic Acids
Recent Patents on Regenerative Medicine The Gut Microbiota and the Emergence of Autoimmunity: Relevance to Major Psychiatric Disorders
Current Pharmaceutical Design Are the Extracelluar Pathways a Conduit for the Delivery of Therapeutics to the Brain?
Current Pharmaceutical Design Lysosomal Storage Diseases and the Blood-Brain Barrier
Current Pharmaceutical Design The Updated Role of the Blood Brain Barrier in Subarachnoid Hemorrhage: From Basic and Clinical Studies
Current Neuropharmacology The Blood Brain Barrier, Mechanisms of Cerebral Edema, and the Use of Anti-Inflammatory and other Anti-Edema Agents in Neuro-Oncology
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry CSF as a Surrogate for Assessing CNS Exposure: An Industrial Perspective
Current Drug Metabolism Personalized Nanoparticles for Cancer Therapy: A Call for Greater Precision
Anti-Cancer Agents in Medicinal Chemistry NK-1 Receptor Antagonists: A New Paradigm in Pharmacological Therapy
Current Medicinal Chemistry Transmucosal Drug Delivery- An Overview
Drug Delivery Letters Protection Mechanisms Against Aβ42 Aggregation
Current Alzheimer Research Brain Delivery Systems via Mechanism Independent of Receptor-Mediated Endocytosis and Adsorptive-Mediated Endocytosis
Current Pharmaceutical Biotechnology Biochemical Markers in CSF of ALS Patients
Current Medicinal Chemistry Imaging and Clinical Features of Neurocutaneous Melanosis in the Pediatric Population
Current Medical Imaging Transport Mechanisms at the Blood-Cerebrospinal-Fluid Barrier: Role of Megalin (LRP2)
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Human ABC Transporters at blood-CNS Interfaces as Determinants of CNS Drug Penetration
Current Pharmaceutical Design Radiopharmaceutical: Revolutionary Agents for Diagnosis
Current Radiopharmaceuticals A Review of Nanocarrier-Based CNS Delivery Systems
Current Drug Delivery Antisense Oligonucleotides in the Treatment of Cerebral Gliomas. Review of Concerning Patents
Recent Patents on CNS Drug Discovery (Discontinued)