Köhler C, Eriksson L G, Flood P R, Hardie J A, Okuno E, Schwarcz R
Department of Neuropharmacology, Astra Alab AB, Södertälje, Sweden.
J Neurosci. 1988 Mar;8(3):975-87. doi: 10.1523/JNEUROSCI.08-03-00975.1988.
Quinolinic acid (QUIN) is a potent endogenous excitotoxin, which has been shown to be present in the brain (Wolfensberger et al., 1983). In order to study the cellular localization of QUIN metabolism in the hippocampus, specific antibodies raised against purified rat liver 3-hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyltransferase (QPRT), the enzymes directly responsible for QUIN synthesis and catabolism, respectively, were used for immunohistochemical studies in the adult male rat. Cells containing 3HAO immunoreactivity (3HAO-i) were present in all subfields of the hippocampal region, including the area dentata, Ammon's horn, the subicular complex, and the entorhinal area. The highest density of 3HAO-i cells was found in the molecular layer of Ammon's horn and in the hilus of area dentata, while the granular cell layer of area dentata and stratum pyramidale of Ammon's horn contained the lowest number of 3HAO-stained cells. A majority of hippocampal 3HAO-i cells were also stained with monoclonal antibodies against glial fibrillary acidic protein (GFAP) or S-100 protein, suggesting that 3HAO-i is present primarily in astrocytes. At the ultrastructural level, 3HAO-i was found to be distributed uniformly throughout the cytoplasm, with intense immunostaining present in the internal and the external layers of the mitochondria. QPRT-i was detected in 3 morphologically distinct cell types present in all parts of the hippocampus. The total number of QPRT-i cells was lower than that of the 3HAO-i cells. QPRT-i cells were relatively numerous in the molecular and radial layers of Ammon's horn, while they occurred only sporadically in stratum pyramidale of Ammon's horn and in the granular cell layer of area dentata. Many QPRT-i cells stained with antibodies against GFAP and S-100, but the proportion of cells in which QPRT was colocalized with these glial marker proteins was lower than that for 3-HAO-i cells. At the ultrastructural level, 2 types of QPRT-i glial cells were detected. The smaller cell type had a diffuse cytoplasmic staining, while the larger cell type, which also contained glial filaments, showed diffuse cytoplasmic staining and intense staining of lysosomal structures. The observation that 3HAO and QPRT only partially coexist in hippocampal glial cells suggests that while synthesis and catabolism of QUIN may occur in the same glial cells, catabolism of QUIN can also take place in cells lacking the synthetic enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)
喹啉酸（QUIN）是一种强效内源性兴奋性毒素，已证实在大脑中存在（Wolfensberger等人，1983年）。为了研究海马体中QUIN代谢的细胞定位，分别针对纯化的大鼠肝脏3-羟基邻氨基苯甲酸加氧酶（3HAO）和喹啉酸磷酸核糖基转移酶（QPRT）（这两种酶分别直接负责QUIN的合成和分解代谢）制备的特异性抗体，被用于成年雄性大鼠的免疫组织化学研究。含有3HAO免疫反应性（3HAO-i）的细胞存在于海马区的所有亚区，包括齿状回、海马角、海马下托复合体和内嗅区。在海马角的分子层和齿状回的门区发现3HAO-i细胞的密度最高，而齿状回的颗粒细胞层和海马角的锥体层中3HAO染色细胞的数量最少。大多数海马3HAO-i细胞也被抗胶质纤维酸性蛋白（GFAP）或S-100蛋白的单克隆抗体染色，这表明3HAO-i主要存在于星形胶质细胞中。在超微结构水平上，发现3HAO-i均匀分布于整个细胞质中，线粒体内外两层有强烈的免疫染色。在海马体各部位存在的3种形态不同的细胞类型中检测到了QPRT-i。QPRT-i细胞的总数低于3HAO-i细胞。QPRT-i细胞在海马角的分子层和放射层中相对较多，而在海马角的锥体层和齿状回的颗粒细胞层中仅偶尔出现。许多QPRT-i细胞被抗GFAP和S-100的抗体染色，但QPRT与这些胶质细胞标记蛋白共定位的细胞比例低于3-HAO-i细胞。在超微结构水平上，检测到2种QPRT-i胶质细胞类型。较小的细胞类型有弥漫性细胞质染色，而较大的细胞类型（也含有胶质丝）则显示弥漫性细胞质染色和溶酶体结构的强烈染色。3HAO和QPRT仅部分共存于海马胶质细胞中的观察结果表明，虽然QUIN的合成和分解代谢可能发生在同一胶质细胞中，但QUIN的分解代谢也可能发生在缺乏合成酶的细胞中。（摘要截取自400字）
