EVIDENCE FOR FUNCTIONALLY IMPORTANT ADENOSINE A(2A) RECEPTORS IN THE RAT HIPPOCAMPUS
EVIDENCE FOR FUNCTIONALLY IMPORTANT ADENOSINE A(2A) RECEPTORS IN THE RAT HIPPOCAMPUS
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DOI：
10.1016/0006-8993(94)91066-9
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发表时间：
1994-06-27
期刊：
影响因子：
2.9
通讯作者：
FREDHOLM, BB
中科院分区：
文献类型：
--
作者：
CUNHA, RA;JOHANSSON, B;FREDHOLM, BB
腺苷A（2a）受体并不局限于大脑富含多巴胺的区域，因为热循环分析表明腺苷A（2a）受体mRNA也在海马（CA 1、CA 3和齿状回）和大脑皮层中表达。原位杂交证实A（2a）mRNA在海马3个主要区域均有表达，A（2a）mRNA主要表达于锥体细胞和颗粒细胞，与腺苷A（1）受体mRNA表达的海马区域相同。用[H-3]CGS 21680（30 nM）（一种选择性腺苷A（2a）受体激动剂）进行的受体放射自显影研究显示，海马中存在特异性结合位点。[H-3]CGS 21680在海马CA 1区放射层结合密度最高，其次是氨角起始层、CA 3区放射层和齿状回颗粒上层。[H-3]CGS 21680结合的解剖学分布与海马中[H-3]CHA结合的模式相似。在Schaffer纤维/CA 1锥体中的电生理学研究表明，在用CGS 21680（10 nM）激活A（2a）受体后，腺苷A（1）受体激动剂CPA抑制神经元活性的能力显著减弱。这些结果显示腺苷A（2a）和A（1）受体在海马中的功能重要的共表达和共定位。结果还表明，腺苷A（2a）受体介导的神经调节不仅限于基底神经节，而是更广泛地分布在整个神经系统。
Adenosine A(2a) receptors are not confined to dopamine-rich areas of the brain, since thermocycling analysis shows that adenosine A(2a) receptor mRNA is expressed also in the hippocampus (CA1, CA3 and dentate gyrus) and cerebral cortex. The expression of A(2a) mRNA in three main areas of the hippocampus was confirmed by in situ hybridization; A(2a) mRNA expression was mainly localized in the pyramidal and granular cells, the same hippocampal regions that showed adenosine A(1) receptor mRNA expression. Receptor autoradiographic studies with [H-3]CGS 21680 (30 nM), a selective adenosine A(2a), receptor agonist, showed specific binding sites in the hippocampus. The density of [H-3]CGS 21680 binding was greatest in the stratum radiatum of the CA1 area, followed by the stratum oriens of the cornu Ammonis, stratum radiatum of the CA3 area and supra-granular layer of the dentate gyrus. This anatomical distribution of [H-3]CGS 21680 binding was similar to the pattern of [H-3]CHA binding in the hippocampus. Electrophysiological studies in the Schaffer fibers/CA1 pyramids showed that upon activation of the A(2a) receptors with CGS 21680 (10 nM) the ability of the adenosine A(1) receptor agonist, CPA, to inhibit neuronal activity was significantly attenuated. These results show functionally important co-expression and co-localization of adenosine A(2a) and A(1) receptors in the hippocampus. The results also suggest that adenosine A(2a) receptor-mediated neuromodulation is not confined to the basal ganglia, but is more widespread throughout the nervous system.