Adenosine A2A-dopamine D2 receptor-receptor heteromers.: Targets for neuro-psychiatric disorders
Adenosine A2A-dopamine D2 receptor-receptor heteromers.: Targets for neuro-psychiatric disorders
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DOI：
10.1016/j.parkreldis.2004.02.014
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发表时间：
2004-07-01
影响因子：
4.1
通讯作者：
Woods, A
中科院分区：
文献类型：
--
作者：
Ferré, S;Ciruela, F;Woods, A
新出现的证据表明，G蛋白偶联受体可以形成同聚体和异聚体。这些包括腺苷A（2A）受体-多巴胺D-2受体异聚体，其最有可能位于纹状体苍白球GABA能神经元的树突棘中，在那里它们处于调节多巴胺能神经传递的位置。A（2A）受体-多巴胺D-2受体异聚体的发现为两种受体之间的众所周知的拮抗相互作用提供了框架，这是神经精神疾病（如帕金森病和帕金森病）的新治疗方法的基础。本文综述了A（2A）受体与多巴胺D-2受体相互作用的生物化学和分子机制。最近在分子水平上的结果表明，A（2A）受体-多巴胺D-2受体异聚体代表了受体异聚化基础上的表位-表位静电相互作用的第一个例子。最有可能的是，A（2A）受体-D-2受体异聚化不是静态的，而是受到动态调节，与A（2A）受体表位的磷酸化依赖性和D-2受体表位结合不同配偶体的能力有关。找出参与这种动态调节的机制对于基底神经节疾病、精神分裂症和药物成瘾的治疗具有重要意义。(C)2004爱思唯尔有限公司保留所有权利。
Emerging evidence show; that G protein-coupled receptors can form homo- and heteromers. These include adenosine A(2A) receptor-dopamine D-2 receptor heteromers, which are most probably localized in the dendritic spines of the striatopallidal GABAergic neurons, where they are in a position to modulate glutamatergic neurotransmission. The discovery of A(2A) receptor-dopamine D-2 receptor heteromers gives a frame for the well-known antagonistic interaction between both receptors, which is the bases for a new therapeutic approach for neuropsychiatric disorders, such as Parkinson's disease and schizoprenia. The present review deals mainly with the biochemical and molecular aspects of A(2A) receptor-dopamine D-2 receptor interactions. Recent results at the molecular level show that A(2A) receptor-dopamine D-2 receptor heteromers represent the first example of epitope-epitope electrostatic interaction underlying receptor heteromerization. Most probably A(2A) receptor-D-2 receptor heteromerization is not static, but subject to a dynamic regulation, related to the phosphorylation dependence of the A(2A) receptor epitope and to the ability of the D-2 receptor epitope to bind different partners. Finding out the mechanisms involved in this dynamic regulation can have important implications for the treatment of basal ganglia disorders, schizophrenia and drug addiction. (C) 2004 Elsevier Ltd. All rights reserved.