Up-regulation of adenosine receptors in the frontal cortex in Alzheimer's disease
Up-regulation of adenosine receptors in the frontal cortex in Alzheimer's disease
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DOI：
10.1111/j.1750-3639.2007.00112.x
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发表时间：
2008-04-01
期刊：
影响因子：
6.4
通讯作者：
Martin, Mairena
中科院分区：
文献类型：
--
作者：
Albasanz, Jose L.;Perez, Sandra;Martin, Mairena
腺苷受体是调节神经递质释放的g蛋白偶联受体，主要是谷氨酸。腺苷A(1)和A（2A）受体在阿尔茨海默病（AD）和年龄匹配对照的死后人类皮层中进行了研究。使用[H-3]DPCPX通过放射配体结合试验测定的总腺苷A(1)受体数量在早期和晚期AD病例中显著增加，但与疾病的进展没有差异。Western blot还发现，在AD的早期和晚期，A(1)R （37 kDa）水平显著升高。此外，通过使用[H-3]ZM 241385作为放射配体的结合试验和Western blot检测，在AD样品中观察到腺苷A（2A）受体的数量增加。腺苷受体结合和蛋白表达水平的增加与编码A(1)和A（2A）受体的mRNA水平的增加无关。最后，观察到A(1)和A（2A）受体介导的反应增加。这些结果表明，AD患者额叶皮质中腺苷A(1)和A（2A）受体的上调与相应转导通路的敏化有关。
Adenosine receptors are G-protein coupled receptors which modulate neurotransmitter release, mainly glutamate. Adenosine A(1) and A(2A) receptors were studied in post-mortem human cortex in Alzheimer's disease (AD) and age-matched controls. Total adenosine A(1) receptor number, determined by radioligand binding assay, using [H-3]DPCPX, was significantly increased in AD cases in early and advanced stages without differences with the progression of the disease. A significant increase of A(1)R (37 kDa) levels was also observed by Western blot in early and advanced stages of AD. In addition, increased numbers of adenosine A(2A) receptors were observed in AD samples as determined by a binding assay using [H-3]ZM 241385 as a radioligand and by Western blot. Increased binding and protein expression levels of adenosine receptors were not associated with increased mRNA levels coding A(1) and A(2A) receptors. Finally, increased A(1) and A(2A) receptor-mediated response was observed. These results show up-regulation of adenosine A(1) and A(2A) receptors in frontal cortex in AD, associated with sensitization of the corresponding transduction pathways.