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Argininosuccinate as a possible neuromodulator and localization of its metabolizing enzymes

精氨基琥珀酸作为一种可能的神经调节剂及其代谢酶的定位

基本信息

批准号：
03807012
负责人：
SAHEKI Takeyori
金额：
$ 1.22万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

From our previous immunohistochemical study on the localization of argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) in the rat brain, we postulate that argininosuccinate may be a novel neuromodulator. It is because some neuronal cells contain ASS, but not ASL, and some others contain ASL, but not ASS. We showed that the activity ratios of ASS to ASL in various tissues varied from about unity in the liver, kidney and testis to nearly zero in the spleen and skeletal muscle. As the whole brain, the ratio was 0.27, but the each nucleus or brain part shows quite a varied value from 0.78 to 0.06. These results suggest that the two enzymes do not always play a role cooperatively in arginine-synthesizing system. In many tissues and cells, arginine-synthesizing system may play a role in supplying arginine for the synthesis of nitric oxide (NO). In the parasympathetic ganglia located in the pancreas, ASS was found in the nerve cells where NO synthase detected as NADP dehydrogenase was located. On the contrary, ASS and NO synthase were differently localized in the neuronal cells of striatum, again suggesting that ASS might synthesize argininosuccinate for secretion from the cells as a neuromodulator. We found that argininosuccinate decreased the response of isolated cerebellar cells to glutamte even at the concentration of 10-10M, but it did not affect the response of cultured olfactory cells to glutamate and of Langerhans islet cells to glucose. Further extensive works are needed for the establishment of argininosuccinate as a neuromodulator.

从我们以前的免疫组织化学研究的定位，乙酰氨基琥珀酸合成酶（ASS）和乙酰氨基琥珀酸裂解酶（ASL）在大鼠脑，我们推测，乙酰氨基琥珀酸可能是一种新的神经调质。这是因为有些神经元细胞含有ASS，但不含ASL，而有些神经元细胞含有ASL，但不含ASS。我们发现，在各种组织中，ASS与ASL的活性比从肝脏、肾脏和睾丸中的约1变化到脾脏和骨骼肌中的几乎为零。整个脑的比值为0.27，但每个核团或脑部分的比值从0.78到0.06不等。这些结果表明，这两种酶在甜菜碱合成系统中并不总是协同作用。在许多组织和细胞中，精氨酸合成系统可能在为一氧化氮（NO）的合成提供精氨酸方面发挥作用。在位于胰腺的副交感神经节中，ASS被发现在神经细胞中，检测到的NADP脱氢酶的NO合酶位于。相反，ASS和NO合酶在纹状体的神经元细胞中的定位不同，再次表明ASS可能作为神经调节剂合成从细胞中分泌的琥珀酸酯。我们发现，即使在10- 10 M的浓度下，琥珀酸单酯也能降低分离的小脑细胞对谷氨酸的反应，但它不影响培养的嗅细胞对谷氨酸的反应和胰岛细胞对葡萄糖的反应。需要进一步广泛的工作来建立作为神经调节剂的乙酰氨基琥珀酸。