MOLECULAR-CLONING OF THE RAT ADENOSINE-A2 RECEPTOR - SELECTIVE COEXPRESSION WITH D2-DOPAMINE RECEPTORS IN RAT STRIATUM
MOLECULAR-CLONING OF THE RAT ADENOSINE-A2 RECEPTOR - SELECTIVE COEXPRESSION WITH D2-DOPAMINE RECEPTORS IN RAT STRIATUM
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DOI：
10.1016/0169-328x(92)90173-9
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发表时间：
1992-07-01
期刊：
影响因子：
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通讯作者：
REPPERT, SM
中科院分区：
文献类型：
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作者：
FINK, JS;WEAVER, DR;REPPERT, SM
利用聚合酶链反应（PCR）方法从大鼠脑中分离出一个与其他G蛋白偶联受体同源的cDNA片段，并证明其在纹状体中大量表达。以该片段为探针，从大鼠纹状体cDNA文库中分离出一个2.1 kb的全长cDNA。该cDNA编码一个含410个氨基酸的蛋白质，与先前分离出的腺苷受体cDNA高度同源。此cDNA在COS细胞中的表达显示出对A2腺苷受体选择性配体[³H]CGS 21680具有高亲和力（Kd = 38.6 nM）和可饱和结合。[³H]CGS 21680结合的激动剂置换曲线与A2亚型腺苷受体一致（NECA >（R）-PIA > CPA >（S）-PIA）。原位杂交表明，大鼠A2腺苷受体mRNA与D2多巴胺受体mRNA在相同的纹状体神经元中共表达，且从不与纹状体D1多巴胺受体mRNA共表达。先前有多条证据表明，多巴胺诱导的运动行为变化可被作用于前脑A2亚型腺苷受体的腺苷类似物所调节。D2多巴胺和A2腺苷受体在一部分纹状体细胞中的共表达为运动行为上的多巴胺能 - 腺苷能相互作用提供了解剖学基础。
A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (K(d) = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [H-3]CGS 21680. Agonist displacement profile of [H-3]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA > (R)-PIA > CPA > (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior.