Svenningsson P, Le Moine C, Kull B, Sunahara R, Bloch B, Fredholm B B
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1997 Oct;80(4):1171-85. doi: 10.1016/s0306-4522(97)00180-2.
The cellular distribution of adenosine A2A receptor messenger RNA in the central nervous system was investigated using in situ hybridization with ribonucleotide probes. A specific expression was found in the dorsal (i.e. caudate putamen) and ventral (i.e. nucleus accumbens and olfactory tubercle) striatum, the lateral septum and in some cerebellar Purkinje cells. Simultaneous detection of radioactive and non-radioactive probes showed that the majority of adenosine A2A receptor messenger RNA-containing neurons in the dorsal and ventral striatum co-expressed dopamine D2 receptor messenger RNA and preproenkephalin A messenger RNA. However, a minor sub-population of neurons expressing adenosine A2A receptor messenger RNA, but not preproenkephalin A messenger RNA, was found in clusters along the ventral border of the nucleus accumbens. Only a small number of striatal neurons expressing dopamine D1 receptor or substance P messenger RNAs also expressed adenosine A2A receptor messenger RNA. Finally, in the ventral part of nucleus accumbens and in the olfactory tubercle a major sub-population of neurons expressed preproenkephalin A messenger RNA, but not adenosine A2A receptor messenger RNA. Cholinergic interneurons did not express adenosine A2A receptor messenger RNA. Thus, the extensive co-localization of adenosine A2A and dopamine D2 receptors previously described in the dorsal striatum extends into its ventral part. There is also a high degree of co-expression of adenosine A2A receptor messenger RNA and preproenkephalin A messenger RNA in the ventral striatum, but within this region several topologically defined sub-populations of neurons express only one of these transcripts. A majority of the adenosine A2A receptor messenger RNA-containing neurons in the lateral septum did contain preproenkephalin A messenger RNA, whereas only a few co-expressed dopamine D2 receptor messenger RNA. This detailed investigation demonstrates that most of the subcortical areas innervated by dopamine have an abundant, although restricted expression of the adenosine A2A receptor gene and that this receptor is expressed in very few cells outside these areas. These results predict that adenosine A2A receptors are involved not only in motor behaviour, but also in goal-oriented behaviours.
利用核糖核苷酸探针原位杂交技术，研究了腺苷A2A受体信使核糖核酸在中枢神经系统中的细胞分布。在背侧（即尾状壳核）和腹侧（即伏隔核和嗅结节）纹状体、外侧隔以及一些小脑浦肯野细胞中发现了特异性表达。放射性和非放射性探针的同时检测表明，背侧和腹侧纹状体中大多数含有腺苷A2A受体信使核糖核酸的神经元同时表达多巴胺D2受体信使核糖核酸和前脑啡肽原A信使核糖核酸。然而，在伏隔核腹侧边界沿线的簇中发现了一小部分表达腺苷A2A受体信使核糖核酸但不表达前脑啡肽原A信使核糖核酸的神经元亚群。只有少数表达多巴胺D1受体或P物质信使核糖核酸的纹状体神经元也表达腺苷A2A受体信使核糖核酸。最后，在伏隔核腹侧部分和嗅结节中，大部分神经元表达前脑啡肽原A信使核糖核酸，但不表达腺苷A2A受体信使核糖核酸。胆碱能中间神经元不表达腺苷A2A受体信使核糖核酸。因此，先前在背侧纹状体中描述的腺苷A2A和多巴胺D2受体的广泛共定位延伸到其腹侧部分。在腹侧纹状体中，腺苷A2A受体信使核糖核酸和前脑啡肽原A信使核糖核酸也有高度的共表达，但在该区域内，几个拓扑定义的神经元亚群只表达这些转录本中的一种。外侧隔中大多数含有腺苷A2A受体信使核糖核酸的神经元确实含有前脑啡肽原A信使核糖核酸，而只有少数同时表达多巴胺D2受体信使核糖核酸。这项详细研究表明，多巴胺支配的大多数皮质下区域虽然腺苷A2A受体基因表达受限，但表达丰富，并且该受体在这些区域之外的细胞中表达极少。这些结果预测，腺苷A2A受体不仅参与运动行为，还参与目标导向行为。
