Anomalous properties of [3H]spiperone binding sites in various areas of the rat limbic system.
Anomalous properties of [3H]spiperone binding sites in various areas of the rat limbic system.
复制标题
大鼠边缘系统各个区域[3H]螺哌酮结合位点的异常特性。
作者：
D. Howlett;H. Morris;S. Nahorski
[3H]Spiperone是一种抗精神病药/多巴胺受体配体，以高亲和力（Kd 0.15 nM）结合大鼠纹状体膜上的单个特异性位点。“特异性”结合约占总结合的80%，并被多巴胺、阿波啡和立体特异性神经抑制剂（如丁他卡莫和氟哌辛醇）取代。然而，与纹状体相反，只有30-40%的[3H]spiperone与边缘前脑膜的结合被丁他卡莫或氟哌辛醇立体特异性地取代，而多巴胺和某些spiperone类似物以高亲和力竞争约70%的标记位点。这些附加的位点是饱和的、可逆的和高亲和力的。结合和解离速率的动力学分析得出Kd值（1.5 nM）与这些位点的平衡饱和数据一致。它们也具有精确的分布，在海马体、隔和伏隔核中发现大量，但在纹状体、嗅结节和下丘脑等区域完全没有。此外，这些[3H]spiperone结合位点表现出严格的结构亲和力关系，只有spirodecanone - butyrophenone衍生物和多巴胺能够以相对高的亲和力取代这种结合。这些结果强调了大脑中抗精神病药/多巴胺“受体”结合位点的复杂性，以及对这种“特异性”结合位点进行精确定义的必要性。
[3H]Spiperone, a neuroleptic/dopamine receptor ligand, binds with high affinity (Kd 0.15 nM) to a single specific site on rat corpus striatum membranes. The "specific" binding represents about 80% of the total binding and is displaced by dopamime, apomorphine, and stereospecifically by neuroleptics such as butaclamol and flupenthixol. However, in contrast to the striatum, only 30-40% of the binding of [3H]spiperone to limbic forebrain membranes is displaced stereospecifically by butaclamol or flupenthixol, whereas dopamine and certain spiperone analogues compete with high affinity for about 70% of the labeled sites. These additional sites are saturable, reversible, and of high affinity. Kinetic analysis of association and dissociation rates yields a Kd value (1.5 nM) in agreement with equilibrium saturation data for these sites. They also possess a precise distribution, with high amounts being found in the hippocampus, septum, and nucleus accumbens, but they are completely absent in areas such as the corpus striatum, olfactory tubercles and hypothalamus. Moreover, these [3H]spiperone binding sites show strict structure-affinity relationships in that only spirodecanone butyrophenone derivatives and dopamine are capable of displacing this binding with relatively high affinities. The results emphasize the complex nature of neuroleptic/dopamine "receptor" binding sites in brain and the need for precise definition of such "specific" binding sites.