Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Brain Res. 2012 Oct 2;1476:108-18. doi: 10.1016/j.brainres.2012.04.051. Epub 2012 May 4.
The striatum is a subcortical area involved in sensorimotor, cognitive and emotional processes. Adenosine A(2A) receptors (A(2A)Rs) are highly expressed in the striatum, and their ability to establish functional and molecular interactions with many other receptors attributes to a pivotal role in the modulation and integration of striatal neurotransmission. This review will focus on the interaction between A(2A)Rs and cannabinoid CB(1) receptors (CB(1)Rs), taking it as a paradigmatic example of synaptic integration. Indeed, A(2A)Rs can exert an opposite (permissive vs. inhibitory) influence on CB1-dependent synaptic effect. These apparently irreconcilable functions could depend on a different role of pre- vs. postsynaptic A(2A)Rs, on their interaction with other receptors (namely adenosine A(1), metabotropic glutamate 5 and dopamine D2 receptors), and on whether A(2A)Rs form or not heteromers with CB(1)Rs. Besides providing a good example of the intricate pattern of events taking place in striatal synapses, the A(2A)/CB(1)R interaction proves very informative to understand the physiology of the basal ganglia and the mechanisms of related diseases. This article is part of a Special Issue entitled: Brain Integration.
纹状体是参与感觉运动、认知和情感过程的皮质下区域。腺苷 A(2A)受体 (A(2A)R) 在纹状体中高度表达，其与许多其他受体建立功能和分子相互作用的能力使其在纹状体神经传递的调节和整合中发挥关键作用。这篇综述将重点讨论 A(2A)R 与大麻素 CB(1)受体 (CB(1)R) 之间的相互作用，将其作为突触整合的典范示例。事实上，A(2A)R 可以对 CB1 依赖性突触效应发挥相反的（允许与抑制）影响。这些看似不可调和的功能可能取决于突触前和突触后 A(2A)R 的不同作用，取决于它们与其他受体（即腺苷 A(1)、代谢型谷氨酸 5 和多巴胺 D2 受体）的相互作用，以及 A(2A)R 是否与 CB(1)R 形成或不形成异源二聚体。除了为纹状体突触中发生的复杂事件模式提供一个很好的例子外，A(2A)/CB(1)R 相互作用还非常有助于理解基底神经节的生理学和相关疾病的机制。本文是题为“大脑整合”的特刊的一部分。
