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Adenosine receptors in the nervous system: pathophysiological implications.
J A Ribeiro1, A M Sebastião, A de Mendonça
1Laboratory of Neurosciences, Faculty of Medicine, Institute for Molecular Medicine, University of Lisbon, Lisbon, Portugal. jaribeiro@neurociencias.pt
Progress in Neurobiology
|February 11, 2003
Summary
Adenosine, a key substance in the brain, modulates neuronal communication via its receptors. Targeting these adenosine receptors shows therapeutic potential for neurological disorders like Parkinson's and Alzheimer's diseases.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Adenosine is a ubiquitous homeostatic substance released by neurones and glia.
- It acts on G-protein-coupled receptors (GPCRs) to modulate neuronal communication, influencing functions like sleep, cognition, and neuronal survival.
- Interactions with other receptor systems allow for fine-tuning of neuronal activity.
Purpose of the Study:
- To explore the multifaceted roles of adenosine receptors in neurological functions.
- To evaluate the therapeutic potential of modulating adenosine receptor activity for neurodegenerative diseases and other neurological conditions.
- To compare the therapeutic utility and side effect profiles of adenosine receptor agonists versus antagonists.
Main Methods:
- Review of existing literature on adenosine receptor function and pharmacology.
- Analysis of the impact of adenosine receptor manipulation on various physiological and pathological processes.
- Examination of clinical and preclinical data regarding adenosine receptor-targeting drugs.
Main Results:
- Adenosine receptor manipulation influences sleep, arousal, cognition, memory, and neuroprotection.
- Adenosine receptor antagonists (e.g., caffeine, theophylline) show promise for Parkinson's and Alzheimer's diseases with fewer side effects than agonists.
- A(1) receptor antagonism may enhance cognition and arousal, while enhancing extracellular adenosine could benefit neuropathic pain.
Conclusions:
- Adenosine acts as a critical fine-tuning modulator of neuronal activity.
- Targeting adenosine receptors offers significant therapeutic potential for a range of neurological disorders.
- Selective antagonism or agonism of adenosine receptors is a promising strategy for treating neurological pathologies when homeostasis is disrupted.