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大鼠新纹状体中的阿片受体:电子显微镜水平的放射自显影分布

Opioid receptors in rat neostriatum: radioautographic distribution at the electron microscopic level.

作者信息

Hamel E, Beaudet A

出版信息

Brain Res. 1987 Jan 20;401(2):239-57. doi: 10.1016/0006-8993(87)91409-0.

DOI:10.1016/0006-8993(87)91409-0
PMID:3028575
Abstract

The distribution of mu-opioid receptors, selectively labeled in vitro with a monoiodinated Met-enkephalin analog [( 125I]FK 33-824), was analyzed by light and electron microscopic radioautography in sections from the neostriatum of the rat. In the light microscope, patches of high receptor densities were detected amidst a moderately labeled matrix. The number of silver grains, as counted in 1-micron thick plastic-embedded sections, was 3 times greater inside the patches than in the intervening matrix. In both compartments, the proportion of labeled binding sites associated with the neuropil was significantly higher (greater than 70%) than that associated with nerve cell bodies or myelinated fascicles. Quantitative analyses of electron microscopic radioautographs revealed that the majority of silver grains corresponding to specifically bound [125I]FK molecules originated from radioactive sources associated with apposed neuronal membranes. Of the total number of specific binding sites, 53% was associated with axodendritic, 18% with axoaxonic and 3% with axosomatic interfaces. The occurrence of multiple labeled foci along the plasma membrane of certain perikarya and dendrites suggested that some of the binding sites might be associated with somato/dendritic elements. The high incidence of labeling along axoaxonic interfaces indicated that others were linked to the membrane of axons and/or axon terminals. A major finding of the present study was that only a small proportion of specific FK binding sites (7% of total) was associated with synaptic junctions. Labeled synapses were primarily of the asymmetric type and were found predominantly on dendritic branches and spines. A few were observed on nerve cell bodies. Labeled symmetric synapses were rare and encountered exclusively on dendritic branches. The high frequency with which specifically labeled binding sites were found to be associated with neuronal interfaces involving axonal processes strongly suggests that even if non-junctional these binding sites correspond to functional receptors. Whether these receptors are activated by endogenous ligand molecules released by the labeled terminals themselves or from terminals located at a distance from the labeled interfaces remains to be determined.

摘要

用单碘化甲硫氨酸脑啡肽类似物[¹²⁵I]FK 33 - 824在体外进行选择性标记的μ-阿片受体,在大鼠新纹状体切片中通过光镜和电镜放射自显影进行分析。在光镜下,在标记程度适中的基质中检测到高受体密度的斑块。在1微米厚的塑料包埋切片中计数的银粒数量,斑块内比其间的基质中多3倍。在两个区域中,与神经毡相关的标记结合位点比例(大于70%)显著高于与神经细胞体或有髓纤维束相关的比例。对电镜放射自显影片的定量分析表明,与特异性结合的[¹²⁵I]FK分子相对应的大多数银粒源自与相邻神经元膜相关的放射源。在总特异性结合位点中,53%与轴-树突、18%与轴-轴和3%与轴-体界面相关。某些胞体和树突的质膜上多个标记灶的出现表明,一些结合位点可能与体/树突成分相关。轴-轴界面上标记的高发生率表明其他位点与轴突和/或轴突终末的膜相连。本研究的一个主要发现是,只有一小部分特异性FK结合位点(占总数的7%)与突触连接相关。标记的突触主要是不对称型,主要见于树突分支和棘上。在神经细胞体上也观察到少数。标记的对称突触很少见,仅见于树突分支上。发现特异性标记的结合位点与涉及轴突过程的神经元界面相关的高频率强烈表明,即使这些结合位点是非连接性的,它们也对应于功能性受体。这些受体是被标记终末自身释放的内源性配体分子激活,还是被位于距标记界面一定距离处的终末释放的内源性配体分子激活,仍有待确定。

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