Margeta-Mitrovic M, Mitrovic I, Riley R C, Jan L Y, Basbaum A I
Department of Physiology, Howard Hughes Medical Institute, University of California San Francisco, 94143, USA.
J Comp Neurol. 1999 Mar 15;405(3):299-321. doi: 10.1002/(sici)1096-9861(19990315)405:3<299::aid-cne2>3.0.co;2-6.
The recent cloning of two gamma-aminobutyric acid(B) (GABA(B)) receptor isoforms (GABA(B)R1a/b), which are probably splice variants of the same gene transcript, allowed us to develop an antiserum that recognized the receptors in fixed tissue and to map their distribution in the rat central nervous system (CNS). We also investigated whether GABA(B)R1 colocalizes with glutamic acid decarboxylase (GAD), a marker of GABAergic cell bodies and terminals. Although GABA(B)R1-like immunoreactivity (GABA(B)R1-LI) was distributed throughout the CNS, several distinct distribution patterns emerged: (1) all monoaminergic brainstem cell groups appeared to contain very high levels of GABA(B)R1, (2) a very high intensity of GABA(B)R1-LI was observed in the majority of the cholinergic regions in the CNS, with exception of motoneurons of the third through sixth cranial nerve nuclei, and (3) a low density of the receptor was observed in most of the nuclei that contain cell bodies of GABAergic projection neurons. The highest GABA(B)R1 labeling was observed in the thalamus, interpeduncular nucleus and medial habenula. Cell bodies were labeled throughout the neuroaxis. We also observed dense neuropil labeling in many regions, suggesting that this receptor is localized in dendrites and/or axon terminals. However, in immunofluorescent double-labeling experiments for GABA(B)R1 and GAD, we never observed GABA(B)R1-LI in GAD-positive axon terminals; this result suggests that the GABA(B)R1 may not function as an autoreceptor. Double labeling was observed in the cell bodies of Purkinje neurons and in some interneurons. In general, the immunohistochemical localization of the GABA(B)R1 correlates well with physiologic and autoradiographic data on the distribution of GABA(B) receptors, but some critical differences were noted. Thus, it is likely that additional GABA(B) receptor subtypes remain to be identified.
最近克隆出了两种γ-氨基丁酸B（GABA(B)）受体亚型（GABA(B)R1a/b），它们可能是同一基因转录本的剪接变体，这使我们能够制备一种抗血清，该抗血清可识别固定组织中的这些受体，并绘制它们在大鼠中枢神经系统（CNS）中的分布图。我们还研究了GABA(B)R1是否与谷氨酸脱羧酶（GAD）共定位，GAD是GABA能细胞体和终末的标志物。尽管GABA(B)R1样免疫反应性（GABA(B)R1-LI）分布于整个中枢神经系统，但出现了几种不同的分布模式：（1）所有单胺能脑干细胞群似乎都含有非常高水平的GABA(B)R1；（2）在中枢神经系统的大多数胆碱能区域观察到非常高强度的GABA(B)R1-LI，但第三至第六脑神经核的运动神经元除外；（3）在大多数含有GABA能投射神经元细胞体的核中观察到该受体的低密度分布。在丘脑、脚间核和内侧缰核中观察到最高的GABA(B)R1标记。细胞体在整个神经轴中都有标记。我们还在许多区域观察到密集的神经纤维网标记，这表明该受体定位于树突和/或轴突终末。然而，在GABA(B)R1和GAD的免疫荧光双标记实验中，我们从未在GAD阳性轴突终末中观察到GABA(B)R1-LI；这一结果表明GABA(B)R1可能不作为自身受体发挥作用。在浦肯野神经元的细胞体和一些中间神经元中观察到双标记。一般来说，GABA(B)R1的免疫组织化学定位与关于GABA(B)受体分布的生理学和放射自显影数据很好地相关，但也注意到了一些关键差异。因此，很可能仍有待鉴定其他GABA(B)受体亚型。
