Pawlak D, Takada Y, Urano T, Takada A
Department of Pharmacodynamics, Medical Academy, Bialystok, Poland.
Brain Res Bull. 2000 Jun;52(3):197-205. doi: 10.1016/s0361-9230(00)00252-5.
Electric foot shock was applied to rats and levels of tryptophan and its metabolites were measured in the plasma, central nervous system and peripheral tissues. Metabolites of tryptophan are the results of the enhancement of serotonergic and kynurenine pathways. Plasma levels of tryptophan increased significantly immediately after the foot shock and returned to normal values within 24 h. Tryptophan levels also increased in all the brain areas immediately after stress application and returned to normal values within 24 h. Foot shock elevated the levels of kynurenine in the plasma, liver, kidney and every parts of the brain. 3-Hydroxykynurenine and kynurenic acid levels were increased in the brain. The present observations suggest that stress activates not only serotonergic pathway but also kynurenine pathway in the central nervous system and periphery. Some metabolites of kynurenine pathway, such as 3-hydroxykynurenine, are neurotoxic while other metabolite, such as kynurenic acid, may be neuroprotective. Increase in serotonin level in the hypothalamus and midbrain stabilises emotion and prevents mood disorders. Therefore, some brain dysfunction resulting from stress may be prevented by the metabolites of tryptophan. The balance of these functions may be important in the maintenance of nerve integrity under stress conditions.
对大鼠施加足部电击，并测定其血浆、中枢神经系统和外周组织中色氨酸及其代谢产物的水平。色氨酸的代谢产物是血清素能途径和犬尿氨酸途径增强的结果。足部电击后，血浆中色氨酸水平立即显著升高，并在24小时内恢复到正常值。应激施加后，所有脑区的色氨酸水平也立即升高，并在24小时内恢复到正常值。足部电击使血浆、肝脏、肾脏和大脑各部位的犬尿氨酸水平升高。大脑中3-羟基犬尿氨酸和犬尿酸水平升高。目前的观察结果表明，应激不仅激活中枢神经系统和外周的血清素能途径，还激活犬尿氨酸途径。犬尿氨酸途径的一些代谢产物，如3-羟基犬尿氨酸，具有神经毒性，而其他代谢产物，如犬尿酸，可能具有神经保护作用。下丘脑和中脑中血清素水平的升高可稳定情绪并预防情绪障碍。因此，应激导致的一些脑功能障碍可能可通过色氨酸的代谢产物来预防。这些功能的平衡对于在应激条件下维持神经完整性可能很重要。
