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Published on: June 20, 2018
[Purinergic regulatory complex in the brain synapses].
Fusao Kato1, Taiko Imura, Eiji Shigetomi
1Laboratory of Neurophysiology, Department of Neuroscience, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461 Japan. fusao@jikei.ac.jp
Adenosine triphosphate (ATP) acts as an extracellular messenger in the central nervous system, modulating synaptic transmission. It triggers glutamate release and suppresses transmitter release via adenosine, forming a purinergic regulatory complex.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Context:
- Synaptic transmission is vital for central nervous system (CNS) function.
- Adenosine triphosphate (ATP) is increasingly recognized for its role as an extracellular messenger at synapses.
- Astrocytes play a key role in releasing ATP into the extracellular space.
Purpose:
- To elucidate the dual role of extracellular ATP and its metabolite adenosine in regulating synaptic transmission.
- To investigate the mechanisms by which ATP and adenosine influence presynaptic neurotransmitter release.
- To define the 'purinergic regulatory complex' governing synaptic signaling.
Summary:
- Extracellular ATP, released by astrocytes, activates presynaptic P2X receptors, triggering glutamate release independently of action potentials.
- ATP is hydrolyzed to adenosine, which then activates presynaptic G protein-coupled receptors, inhibiting voltage-dependent calcium channels and suppressing action potential-driven transmitter release.
- These distinct purinergic signaling pathways operate synergistically in the CNS.
Impact:
- Provides novel insights into the complex regulation of synaptic transmission by purinergic signaling.
- Identifies specific molecular targets (P2X receptors, adenosine receptors) for potential therapeutic interventions in neurological disorders.
- Highlights the synergistic interplay between ATP and adenosine in fine-tuning neuronal communication within the CNS.
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