Van den Pol A N
Section of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06510.
J Comp Neurol. 1994 Nov 22;349(4):615-32. doi: 10.1002/cne.903490409.
The metabotropic glutamate receptor mGluR1 is a G-protein-coupled glutamate receptor whose activation induces phosphotidylinositol hydrolysis and increases diacylglycerol and cytoplasmic calcium. By using affinity-purified antisera against a partial amino acid sequence of mGluR1 alpha, deduced from the nucleotide sequence of the cloned gene, the heterogeneous expression of this glutamate receptor was studied immunocytochemically with light and electron microscopy in the rat hypothalamus. Immunoreactivity was restricted to cell bodies and dendrites throughout many regions of the adult hypothalamus, including the preoptic area, anterior hypothalamus, suprachiasmatic nucleus, dorsomedial hypothalamus, and periventricular region. Strong immunolabeling was found in the lateral hypothalamus where immunoreactivity could be detected as early as embryonic day 18. Intense immunoreactivity was also found in the medial mammillary nuclei. In contrast to the strong labeling in many other regions, the neuroendocrine neurons of the arcuate, supraoptic, and paraventricular nuclei showed relatively little staining in adults. With light microscopy, immunoperoxidase labeling was found distributed in patches on the cytoplasmic side of the plasma membrane of immunoreactive neurons. When the same tissue was examined ultrastructurally, the patches were not restricted to synaptic specializations but were also found distributed on perikaryal and dendritic membranes sometimes associated with synapses and sometimes not. Some immunoreactive membranes showed no immunolabeling at the synaptic junction. When the tissue was strongly stained, labeling could be found in the cytoplasm of immunoreactive cells. No immunostaining was found on axons or presynaptic boutons. Together with other evidence showing a widespread expression of many different subtypes of both ionotropic and metabotropic receptors, these data support the hypothesis that glutamate may regulate hypothalamic cellular activity with a number of physiologically different mechanisms, and these mechanisms include second-messenger systems activated by G proteins.
代谢型谷氨酸受体mGluR1是一种G蛋白偶联型谷氨酸受体，其激活可诱导磷脂酰肌醇水解，并增加二酰基甘油和细胞质钙。利用针对从克隆基因的核苷酸序列推导的mGluR1α部分氨基酸序列的亲和纯化抗血清，通过光镜和电镜免疫细胞化学方法研究了该谷氨酸受体在大鼠下丘脑的异质性表达。免疫反应性局限于成年下丘脑的许多区域的细胞体和树突，包括视前区、下丘脑前部、视交叉上核、下丘脑背内侧核和室周区域。在下丘脑外侧发现了强烈的免疫标记，早在胚胎第18天就可检测到免疫反应性。在内侧乳头核中也发现了强烈的免疫反应性。与许多其他区域的强烈标记形成对比的是，弓状核、视上核和室旁核的神经内分泌神经元在成年动物中染色相对较少。用光镜观察，免疫过氧化物酶标记分布在免疫反应性神经元质膜胞质侧的斑块中。当对同一组织进行超微结构检查时，这些斑块不仅局限于突触特化部位，还发现分布在核周和树突膜上，有时与突触相关，有时则不相关。一些免疫反应性膜在突触连接处没有免疫标记。当组织染色强烈时，在免疫反应性细胞的细胞质中可发现标记。在轴突或突触前终扣上未发现免疫染色。连同其他证据表明离子型和代谢型受体的许多不同亚型广泛表达，这些数据支持这样的假说，即谷氨酸可能通过多种生理上不同的机制调节下丘脑细胞活性，这些机制包括由G蛋白激活的第二信使系统。
