Möhler H, Richards J G, Wu J Y
Proc Natl Acad Sci U S A. 1981 Mar;78(3):1935-8. doi: 10.1073/pnas.78.3.1935.
Benzodiazepine receptors can be visualized in regions of synaptic contact by electron microscopic autoradiography using [3H]flunitrazepam as a photoaffinity label in fresh brain tissue. Perfusion fixation of the tissue prior to photoaffinity labeling left the ligand binding characteristics and the light and electron microscopic distribution of benzodiazepine receptors unaltered. Therefore, the immunocytochemical localization of a neuronal marker in fixed tissue could be combined with photoaffinity labeling in order to identify the types of synapses containing benzodiazepine receptors. By using antiserum to glutamate decarboxylase, a marker of gamma-aminobutyrergic neurons, one-third of the photolabeled benzodiazepine receptors were found to be associated with immunocytochemically stained nerve endings. Thus, these synapses are the site of at lest some benzodiazepine receptors. The enhancement of gamma-aminobutyrergic synaptic transmission by benzodiazepines, shown electrophysiologically, appears to be a primary mechanism of action of this group of drugs.
使用[3H]氟硝西泮作为新鲜脑组织中的光亲和标记,通过电子显微镜放射自显影可在突触接触区域观察到苯二氮䓬受体。在进行光亲和标记之前对组织进行灌注固定,不会改变配体结合特性以及苯二氮䓬受体的光镜和电镜分布。因此,固定组织中神经元标志物的免疫细胞化学定位可与光亲和标记相结合,以识别含有苯二氮䓬受体的突触类型。通过使用针对谷氨酸脱羧酶(γ-氨基丁酸能神经元的标志物)的抗血清,发现三分之一的光标记苯二氮䓬受体与免疫细胞化学染色的神经末梢相关。因此,这些突触至少是部分苯二氮䓬受体的所在部位。电生理学研究表明,苯二氮䓬增强γ-氨基丁酸能突触传递,这似乎是这类药物的主要作用机制。