Bischoff S, Leonhard S, Reymann N, Schuler V, Shigemoto R, Kaupmann K, Bettler B
Novartis Pharma AG, Nervous System, CH-4002 Basel, Switzerland.
J Comp Neurol. 1999 Sep 13;412(1):1-16.
A gamma-aminobutyric acid (GABA)(B) receptor (named GABA(B)R1) has been recently cloned in the rat and human brain and two variants generated by alternative RNA splicing were identified. In the present study, we addressed the question as to whether these variants contribute to the diversity of GABA(B) receptor-mediated physiological responses and constitute real receptor subtypes with distinct functions. To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization. We have compared the mRNA distribution with the distribution of [(3)H]CGP54626-labeled binding GABA(B)R1 receptor sites as assessed in adjacent cryosections by quantitative autoradiography. We found that GABA(B) receptor transcripts and binding sites are expressed in the brain in almost all neuronal cell populations. Expression in glial cells, if any, is marginal. We observed a good parallelism between GABA(B)R1 mRNA transcripts and binding sites in broad neuroanatomical entities with highest densities in hippocampus, thalamic nuclei, and cerebellum. By contrast, R1a and R1b transcripts exhibit marked differences in their regional and cellular distribution pattern. A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells. Data pointing at a pre- versus postsynaptic localization for R1a and R1b, respectively, at some neuronal sites are presented.
一种γ-氨基丁酸（GABA）（B）受体（命名为GABA（B）R1）最近已在大鼠和人类大脑中克隆出来，并鉴定出由可变RNA剪接产生的两种变体。在本研究中，我们探讨了这些变体是否有助于GABA（B）受体介导的生理反应的多样性，并构成具有不同功能的真正受体亚型这一问题。为此，我们使用原位杂交技术绘制了大鼠大脑中GABA（B）R1（R1a）和GABA（B）R1b（R1b）转录本的分布图。我们将mRNA分布与通过定量放射自显影在相邻冷冻切片中评估的[（3）H]CGP54626标记的结合GABA（B）R1受体位点的分布进行了比较。我们发现GABA（B）受体转录本和结合位点在大脑中几乎所有神经元细胞群体中均有表达。在胶质细胞中的表达（如果有的话）微乎其微。我们观察到在广泛的神经解剖实体中，GABA（B）R1 mRNA转录本与结合位点之间具有良好的平行性，在海马体、丘脑核和小脑中密度最高。相比之下，R1a和R1b转录本在其区域和细胞分布模式上表现出明显差异。一个典型的例子是小脑，R1b几乎只在浦肯野细胞中表达，而R1a在颗粒细胞、星状细胞和篮状细胞中表达。本文还提供了一些数据，表明在某些神经元部位，R1a和R1b分别定位于突触前和突触后。
