Argininosuccinate as a possible neuromodulator and localization of its metabolizing enzymes

根据我们之前对大鼠大脑中精氨酸琥珀酸合成酶（ASS）和精氨酸琥珀酸裂解酶（ASL）定位的免疫组化研究，我们假设精氨酸琥珀酸可能是一种新的神经调节剂。这是因为一些神经元细胞含有ASS，而不含ASL，而另一些细胞含有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、肾脏和睾丸的约为1到脾脏和骨骼肌的几乎为零。整个大脑的比率为0.27，但每个核或大脑部分的数值相差很大，从0.78到0.06不等。这些结果表明，这两种酶在精氨酸合成系统中并不总是协同发挥作用。在许多组织和细胞中，精氨酸合成系统可能为一氧化氮（NO）的合成提供精氨酸。在位于胰腺的副交感神经节中，在检测为NADP脱氢酶的NO合酶所在的神经细胞中发现了ASS。相反，ASS和NO合成酶在纹状体神经元细胞中的定位不同，再次提示ASS可能合成精氨酸琥珀酸盐作为神经调节剂从细胞分泌。我们发现精氨酸琥珀酸盐即使在10-10M浓度下也能降低离体小脑细胞对谷氨酸的反应，但不影响培养嗅觉细胞对谷氨酸的反应和朗格汉斯胰岛细胞对葡萄糖的反应。进一步广泛的工作需要建立精氨酸琥珀酸作为一种神经调节剂。

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.