Jomary C, Gairin J E, Beaudet A
Montreal Neurological Institute, McGill University, PQ, Canada.
Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):564-8. doi: 10.1073/pnas.89.2.564.
Distribution of kappa opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective 125I-labeled dynorphin analog [D-Pro10]dynorphin-(1-11). Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (i) the high frequency with which labeled interfaces implicated a dendrite, (ii) the enrichment of dendro-dendritic interfaces, and (iii) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the kappa opioid-induced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. Although most membrane-associated kappa sites were found at extrasynaptic locations, approximately 23% were associated with synaptic specializations. This proportion is markedly higher than that previously reported for either mu or delta sites in rat neostriatum. Whether labeled synapses represent preferential sites of action for kappa ligands remains to be established. In any event, these results support the hypothesis that in mammalian brain kappa opioid receptors are conformationally and functionally distinct from mu and delta types.
采用选择性125I标记的强啡肽类似物[D-脯氨酸10]强啡肽-(1-11)，通过电子显微镜放射自显影术研究豚鼠新纹状体切片中κ阿片受体的分布。通过概率圆分析发现，大多数特异性标记的结合位点与神经元膜并列相关。由于该方法分辨率的限制，无法直接将放射源归属于并列的任何一个质膜。然而，有三条证据支持配体主要与纹状体内在神经元的树突相关：(i)标记界面涉及树突的高频出现；(ii)树突-树突界面的富集；(iii)沿其质膜在几个接触点处标记的树突轮廓的出现。一小部分标记位点与轴突-轴突界面相关，这可能有助于κ阿片诱导的豚鼠新纹状体中突触前多巴胺和乙酰胆碱释放的调节。虽然大多数与膜相关的κ位点位于突触外位置，但约23%与突触特化相关。这个比例明显高于先前报道的大鼠新纹状体中μ或δ位点的比例。标记的突触是否代表κ配体的优先作用位点仍有待确定。无论如何，这些结果支持了这样的假设，即在哺乳动物大脑中，κ阿片受体在构象和功能上与μ和δ类型不同。
