An essential role for adenosine signaling in alcohol abuse.
An essential role for adenosine signaling in alcohol abuse.
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DOI：
10.2174/1874473711003030163
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Choi DS
中科院分区：
文献类型：
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作者：
Ruby CL;Adams CA;Knight EJ;Nam HW;Choi DS
在中枢神经系统（CNS）中，腺苷在调节神经元活动和调节其他神经递质（包括GABA、谷氨酸和多巴胺）的信号传导中起重要作用。腺苷抑制神经递质释放，降低神经元兴奋性，并通过激活四类G蛋白偶联受体A1、A2 A、A2 B和A3调节离子通道功能。中心腺苷水平主要由核苷转运体控制，其调节跨质膜的腺苷水平。腺苷已被证明可调节皮质谷氨酸信号传导和腹侧被盖多巴胺能信号传导，这涉及酒精使用障碍的几个方面。急性乙醇通过选择性抑制1型平衡型核苷转运蛋白ENT 1提高细胞外腺苷水平。腺苷水平升高通过激活小脑、纹状体和大脑皮层中的A1受体介导乙醇的共济失调和镇静/催眠作用。最近，我们已经表明，药物抑制或基因删除ENT 1减少兴奋性氨基酸转运蛋白2（EAAT 2），细胞外谷氨酸的主要调节剂，在星形胶质细胞的表达。这些证据支持了腺苷介导的谷氨酸信号传导的核心作用，以及星形胶质细胞参与调节乙醇中毒和偏好。在本文中，我们讨论了最近的研究结果的影响腺苷信号在酒精使用障碍。
In the central nervous system (CNS), adenosine plays an important role in regulating neuronal activity and modulates signaling by other neurotransmitters, including GABA, glutamate, and dopamine. Adenosine suppresses neurotransmitter release, reduces neuronal excitability, and regulates ion channel function through activation of four classes of G protein-coupled receptors, A1, A2A, A2B, and A3. Central adenosine levels are largely controlled by nucleoside transporters, which regulate adenosine levels across the plasma membrane. Adenosine has been shown to modulate cortical glutamate signaling and ventral-tegmental dopaminergic signaling, which are involved in several aspects of alcohol use disorders. Acute ethanol elevates extracellular adenosine levels by selectively inhibiting the type 1 equilibrative nucleoside transporter, ENT1. Raised adenosine levels mediate the ataxic and sedative/hypnotic effects of ethanol through activation of A1 receptors in the cerebellum, striatum, and cerebral cortex. Recently, we have shown that pharmacological inhibition or genetic deletion of ENT1 reduces the expression of excitatory amino acid transporter 2 (EAAT2), the primary regulator of extracellular glutamate, in astrocytes. These lines of evidence support a central role for adenosine-mediated glutamate signaling and the involvement of astrocytes in regulating ethanol intoxication and preference. In this paper, we discuss recent findings on the implication of adenosine signaling in alcohol use disorders.