Hevor T K, Aissi E, Delorme P
Laboratoire de Neurobiologie Fonctionnelle, Université des Sciences et Techniques de Lille Flandres-Artois, Villeneuve d'Ascq, France.
Neurochem Res. 1990 Sep;15(9):861-8. doi: 10.1007/BF00965904.
This work shows that the convulsant methionine sulfoximine induces an increase in glucose and glycogen levels and a parallel decrease in norepinephrine and dopamine levels in rat brain. Among the epileptogenic agents, methionine sulfoximine is known to have a glycogenic property in the central nervous system. The aim of this work is to look for the neurochemical mechanism underlying this property. For this, catecholamines, glucose, and glycogen were measured at the same time in different areas of the brain in rats submitted to methionine sulfoximine. The convulsant induced an increase in glucose and glycogen levels as previously described and a decrease in dopamine and norepinephrine levels in all the areas of the rat brain. These changes were roughly dose dependent. When L-dihydroxyphenylalanine and benserazide (a decarboxylase inhibitor) were administered with methionine sulfoximine, the latter failed to induce seizures in rat up to 8 h after dosing. Moreover, the glucose and glycogen amounts did not increase. In all these experiments, there was an obvious evidence of parallelism between seizures, increase in carbohydrate levels, and decrease in catecholamine levels. These results allow to conclude that the glycogenic property of methionine sulfoximine in the central nervous system probably results from its ability to decrease norepinephrine and dopamine levels. Because the effect of the convulsant on the catecholamine levels persisted for long, it is normal that glucose and glycogen levels increased during preconvulsive, convulsive and postconvulsive period. Methionine sulfoximine is probably glycogenic in rat brain because it decreases catecholamine levels for a long time.
这项研究表明，惊厥剂蛋氨酸亚砜亚胺可导致大鼠脑内葡萄糖和糖原水平升高，同时去甲肾上腺素和多巴胺水平相应降低。在致癫痫药物中，蛋氨酸亚砜亚胺在中枢神经系统具有糖原生成特性。本研究旨在探寻这一特性背后的神经化学机制。为此，在给予蛋氨酸亚砜亚胺的大鼠脑内不同区域同时测定儿茶酚胺、葡萄糖和糖原水平。结果显示，惊厥剂如前文所述可使大鼠脑内所有区域的葡萄糖和糖原水平升高，多巴胺和去甲肾上腺素水平降低。这些变化大致呈剂量依赖性。当与蛋氨酸亚砜亚胺同时给予L - 二羟基苯丙氨酸和苄丝肼（一种脱羧酶抑制剂）时，给药后长达8小时大鼠未出现惊厥。此外，葡萄糖和糖原含量也未增加。在所有这些实验中，惊厥、碳水化合物水平升高和儿茶酚胺水平降低之间存在明显的平行关系。这些结果表明，蛋氨酸亚砜亚胺在中枢神经系统的糖原生成特性可能源于其降低去甲肾上腺素和多巴胺水平的能力。由于惊厥剂对儿茶酚胺水平的影响持续时间较长，因此在惊厥前、惊厥中和惊厥后期间葡萄糖和糖原水平升高是正常的。蛋氨酸亚砜亚胺在大鼠脑内可能具有糖原生成特性，因为它可长时间降低儿茶酚胺水平。
