GABA(A), GABA(C), AND NMDA RECEPTOR SUBUNIT EXPRESSION IN THE SUPRACHIASMATIC NUCLEUS AND OTHER BRAIN-REGIONS
GABA(A), GABA(C), AND NMDA RECEPTOR SUBUNIT EXPRESSION IN THE SUPRACHIASMATIC NUCLEUS AND OTHER BRAIN-REGIONS
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DOI：
10.1016/0169-328x(94)00212-w
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发表时间：
1995-02-01
期刊：
影响因子：
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通讯作者：
KILDUFF, TS
中科院分区：
文献类型：
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作者：
OHARA, BF;ANDRETIC, R;KILDUFF, TS
视交叉上核（SCN）内神经递质受体亚型的鉴定将进一步了解生物钟的机制，并可能提供药理学操纵昼夜节律的靶点。我们集中在离子型GABA和谷氨酸受体，因为这些似乎占了SCN中的突触通讯的大部分。在哺乳动物中已知编码GABA受体亚基的15个基因中，我们已经检查了SCN中12个基因的表达，仅忽略α 6，γ 3和ρ 2亚基。在谷氨酸受体中，我们集中于编码NMDA受体亚基的五个已知基因，以及帮助组成红藻氨酸选择性受体的两个亚基。通过用从大量小鼠SCN纯化的RNA进行北方分析表征表达，并与剩余的下丘脑、皮质和小脑中的表达进行比较。这种方法提供了一个统一的RNA来源，以产生许多重复的印迹，其中每一个都被反复探测。SCN中最丰富的GABA受体亚基mRNA为α 2、α 5、β 1、β 3、γ 1和γ 2。rho 1（rho 1）亚基产生GABA（C）药理学，主要在三种不同物种的视网膜中表达，尽管与视网膜有共同的胚胎起源，但在小鼠SCN中未检测到。对于几个GABA亚基，我们检测到以前没有描述的额外的mRNA种类。在SCN中还发现了编码谷氨酸脱羧酶的两个基因（GAD（65）和GAD（67））的高表达。在NMDA受体亚基中，NR1在SCN中表达最高，其次是NR2B、NR2A、NR2C和NR2D。此外，GluR5和GluR6均在SCN中显示明确表达，GluRS是最具SCN特异性的。这种方法提供了一个简单的措施受体亚型表达，补充原位杂交研究，并可能提出新的亚型已知的亚基。
Identification of the neurotransmitter receptor subtypes within the suprachiasmatic nuclei (SCN) will further understanding of the mechanism of the biological clock and may provide targets to manipulate circadian rhythms pharmacologically. We have focused on the ionotropic GABA and glutamate receptors because these appear to account for the majority of synaptic communication in the SCN. Of the 15 genes known to code for GABA receptor subunits in mammals we have examined the expression of 12 in the SCN, neglecting only the alpha 6, gamma 3, and rho 2 subunits. Among glutamate receptors, we have focused on the five known genes coding for the NMDA receptor subunits, and two subunits which help comprise the kainate-selective receptors. Expression was characterized by Northern analysis with RNA purified from a large number of mouse SCN and compared to expression in the remaining hypothalamus, cortex and cerebellum. This approach provided a uniform source of RNA to generate many replicate blots, each of which was probed repeatedly. The most abundant GABA receptor subunit mRNAs in the SCN were alpha 2, alpha 5, beta 1, beta 3, gamma 1 and gamma 2. The rho 1 (rho1) subunit, which produces GABA(C) pharmacology, was expressed primarily in the retina in three different species and was not detectable in the mouse SCN despite a common embryological origin with the retina. For several GABA subunits we detected additional mRNA species not previously described. High expression of both genes coding for glutamic acid decarboxylase (GAD(65) and GAD(67)) was also found in the SCN. Among the NMDA receptor subunits, NR1 was most highly expressed in the SCN followed in order of abundance by NR2B, NR2A, NR2C and NR2D. In addition, both GluR5 and GluR6 show clear expression in the SCN, with GluRS being the most SCN specific. This approach provides a simple measure of receptor subtype expression, complements in situ hybridization studies, and may suggest novel isoforms of known subunits.