Faull R L, Villiger J W
Department of Anatomy, School of Medicine, University of Auckland, New Zealand.
Neuroscience. 1988 Feb;24(2):433-51. doi: 10.1016/0306-4522(88)90340-5.
The pharmacological characteristics and anatomical distribution of benzodiazepine receptors in the striatum (dorsal striatum, comprising the caudate nucleus and putamen, and ventral striatum) and globus pallidus (dorsal pallidum, comprising the external and internal segments, and ventral pallidum) of the human basal ganglia were examined in twelve cases aged 4-71 years. The pharmacology of the receptors was studied using computerized, non-linear least-squares regression analysis of [3H]flunitrazepam displacement by flunitrazepam, CL218,872 and ethyl beta-carboline-3-carboxylate binding to membranes. The results showed that the dorsal striatum (caudate nucleus and putamen) contained higher concentrations of receptors than the dorsal pallidum (external and internal segments). The dorsal striatum contained equal numbers of sites with high affinity (Type I) and low affinity (Type II) for CL218,872 and ethyl beta-carboline-3-carboxylate whereas the globus pallidus contained sites with only high affinity (Type I) for these ligands. The anatomical localization of the benzodiazepine receptor subtypes (Type I and II) was studied using quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam in the absence or presence of the discriminating ligand CL218,872. The autoradiograms showed that benzodiazepine receptors were distributed throughout all regions of the human striatum in a heterogeneous fashion, i.e. high-density patches of receptors were set against a background matrix of lower receptor densities. The highest densities of receptors were seen in the ventral striatum where the patches were particularly extensive and showed densities 56% higher than the receptor densities in the dorsal striatal patches. Quantitative analysis showed that the patches in all striatal regions contained mainly Type II receptors (83%-86%) whereas the matrix regions in the ventral and dorsal striatum contained different proportions of the receptor subtypes; Type I receptors predominated (60%) in the matrix of the ventral striatum and Type II receptors predominated (67%-71%) in the matrix of the dorsal striatum. By contrast, the autoradiograms showed that the globus pallidus contained considerably lower concentrations of receptors than the striatum. The highest density of receptors in the globus pallidus was present in the ventral pallidum with successively lower concentrations in the external (26% less) and internal (66% less) segments of the dorsal pallidum. In agreement with the membrane binding studies the receptors in the globus pallidus were mainly of the Type I variety.(ABSTRACT TRUNCATED AT 400 WORDS)
在12例年龄在4至71岁的患者中，研究了人类基底神经节的纹状体（背侧纹状体，包括尾状核和壳核，以及腹侧纹状体）和苍白球（背侧苍白球，包括外侧段和内侧段，以及腹侧苍白球）中苯二氮䓬受体的药理学特性和解剖分布。通过对[³H]氟硝西泮、CL218,872和β-咔啉-3-羧酸乙酯与膜结合的计算机化非线性最小二乘回归分析，研究了受体的药理学。结果表明，背侧纹状体（尾状核和壳核）中的受体浓度高于背侧苍白球（外侧段和内侧段）。背侧纹状体中对CL218,872和β-咔啉-3-羧酸乙酯具有高亲和力（I型）和低亲和力（II型）的位点数量相等，而苍白球中对这些配体仅具有高亲和力（I型）的位点。在不存在或存在区分性配体CL218,872的情况下，用[³H]氟硝西泮对冰冻切片进行体外标记后，使用定量放射自显影法研究了苯二氮䓬受体亚型（I型和II型）的解剖定位。放射自显影片显示，苯二氮䓬受体以异质性方式分布在人类纹状体的所有区域，即高密度的受体斑块与较低受体密度的背景基质相对。在腹侧纹状体中观察到最高的受体密度，其中斑块特别广泛，其密度比背侧纹状体斑块中的受体密度高56%。定量分析表明，所有纹状体区域的斑块主要包含II型受体（83%-86%），而腹侧和背侧纹状体的基质区域包含不同比例的受体亚型；I型受体在腹侧纹状体基质中占主导（60%），II型受体在背侧纹状体基质中占主导（67%-71%）。相比之下，放射自显影片显示，苍白球中的受体浓度明显低于纹状体。苍白球中最高的受体密度出现在腹侧苍白球，背侧苍白球的外侧段（低26%）和内侧段（低66%）中的浓度依次降低。与膜结合研究一致，苍白球中的受体主要是I型。（摘要截断于400字）
