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首页> 外文期刊>The European Journal of Neuroscience >GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization.
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GABAB-receptor splice variants GB1a and GB1b in rat brain: developmental regulation, cellular distribution and extrasynaptic localization.

机译:大鼠脑中的GABA B受体剪接变体GB1a和GB1b:发育调节,细胞分布和突触外定位。

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摘要

GABAB (gamma-aminobutyric acid)-receptors have been implicated in central nervous system (CNS) functions, e.g. cognition and pain perception, and dysfunctions including spasticity and absence epilepsy. To permit an analysis of the two known GABAB-receptor splice variants GABAB-R1a (GB1a) and GABAB-R1b (GB1b), their distribution pattern has been differentiated in the rat brain, using Western blotting and immunohistochemistry with isoform-specific antisera. During postnatal maturation, the expression of the two splice variants was differentially regulated with GB1a being preponderant at birth. In adult brain, GB1b-immunoreactivity (-IR) was predominant, and the two isoforms largely accounted for the pattern of GABAB-receptor binding sites in the brain. Receptor heterogeneity was pronounced in the hippocampus, where both isoforms occurred in CA1, but only GB1b in CA3. Similarly, in the cerebellum, GB1b was exclusively found in Purkinje cells in a zebrin-like pattern. The staining was most pronounced in Purkinje cell dendrites and spines. Using electron microscopy, over 80% of the spine profiles in which a synaptic contact with a parallel fibre was visible contained GB1b-IR at extrasynaptic sites. This subcellular localization is unrelated to GABAergic inputs, indicating that the role of GABAB-receptors in vivo extends beyond synaptic GABAergic neurotransmission and may, in the cerebellum, involve taurine as a ligand.
机译:GABAB(γ-氨基丁酸)受体已经牵涉到中枢神经系统(CNS)功能,例如认知和疼痛知觉,以及包括痉挛和失神癫痫的功能障碍。为了对两种已知的GABAB-受体剪接变体GABAB-R1a(GB1a)和GABAB-R1b(GB1b)进行分析,使用蛋白质印迹法和同工型特异性抗血清免疫组化技术,在大鼠大脑中对它们的分布模式进行了区分。在产后成熟期间,两个剪接变体的表达受到差异调节,其中GB1a在出生时占优势。在成年大脑中,GB1b免疫反应性(-IR)是主要的,这两种同工型在很大程度上说明了大脑中GABAB受体结合位点的模式。受体异质性在海马区明显,其中两个同工型都出现在CA1中,而在CA3中仅出现GB1b。类似地,在小脑中,GB1b仅以斑马蛋白样模式存在于Purkinje细胞中。染色在浦肯野细胞树突和棘中最为明显。使用电子显微镜检查,可以看到超过80%的脊柱轮廓在突触外位点包含GB1b-IR。这种亚细胞定位与GABA能输入无关,表明体内GABA B受体的作用超出了突触GABA能神经传递,在小脑中可能包含牛磺酸作为配体。

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