[3H]-nociceptin ligand-binding and nociceptin opioid receptor mRNA expression in the human brain
[3H]-nociceptin ligand-binding and nociceptin opioid receptor mRNA expression in the human brain
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DOI：
10.1016/s0306-4522(03)00484-6
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发表时间：
2003-01-01
期刊：
影响因子：
3.3
通讯作者：
Tölle, TR
中科院分区：
文献类型：
--
作者：
Berthele, A;Platzer, S;Tölle, TR
随着新型痛觉肽阿片受体（NOP1）的克隆及其内源性配体孤啡肽FQ/痛觉肽的鉴定，人们主要研究了NOP1受体系统在啮齿动物中枢神经系统中的分布和功能作用。本研究采用[H-3]-nociceptin放射自显影技术、NOP1逆转录酶PCR和mRNA原位杂交技术研究了成人脑组织中NOP1受体的区域分布和剪接变异表达。配体结合表明，大脑皮层功能性NOP1受体表达强烈，海马和小脑信号中等。有趣的是，NOP1受体特异性配体在人类纹状体中也被强烈结合。在前额叶和扣带皮层以及海马齿状回中观察到大量NOP1 mRNA表达的匹配模式。在纹状体中，阿蒙角和小脑皮层的mRNA水平为中低水平。通过原位杂交，在人脑中未检测到n端NOP1剪接变体mrna的大量表达。这表明人脑中功能性NOP1受体是由n端全长NOP1转录本编码的。关于痛觉肽结合位点和NOP1受体mRNA的解剖分布的数据有助于了解人脑中的阿片受体系统，并可能促进对人类中枢神经系统中孤儿蛋白FQ/痛觉肽受体系统的功能和药理学的理解。(C) 2003年由Elsevier Ltd代表IBRO出版。
Following the cloning of the novel nociceptin opioid receptor (NOP1) and the identification of its endogenous ligand orphanin FQ/nociceptin the distribution and functional role of the NOP1 receptor system have been studied mainly in the rodent CNS. In the present study the regional distribution and splice variant expression of the NOP1 receptor was investigated in the adult human brain using [H-3]-nociceptin autoradiography, NOP1 reverse transcriptase PCR and mRNA in situ hybridization.Ligand binding revealed strong expression of functional NOP1 receptors in the cerebral cortex and moderate signals in hippocampus and cerebellum. Interestingly, the NOP1 receptor specific ligand was also strongly bound in the human striatum. A matching pattern of mRNA expression was observed with high amounts of NOP1 mRNA in the prefrontal and cingulate cortex as well as in the dentate gyrus of the hippocampus. mRNA levels in the Ammon's horn and cerebellar cortex were moderate and low in the striatum. A considerable expression of N-terminal NOP1 splice variant mRNAs was not detectable in the human brain by means of in situ hybridization. This suggests that functional NOP1 receptors in the human brain are encoded by N-terminal full length NOP1 transcripts.The present data on the anatomical distribution of nociceptin binding sites and NOP1 receptor mRNA contribute to the knowledge about opioid receptor systems in the human brain and may promote the understanding of function and pharmacology of the orphanin FQ/nociceptin receptor system in the human CNS. (C) 2003 Published by Elsevier Ltd on behalf of IBRO.