Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
Chirality. 2011;23 Suppl 1:E12-5. doi: 10.1002/chir.20938. Epub 2011 Mar 23.
Kynurenic acid (KYNA), an endogenous antagonist of N-methyl-D-aspartate and α(7) nicotinic acetylcholine receptors, is one of the L-tryptophan (Trp) metabolites. To compare the level of KYNA produced in the striatum of rats after independent administration of L-Trp and D-Trp, rats were intraperitoneally administered L-Trp and/or D-Trp (100 mg/kg), and a microdialysis (MD) probe was implanted in the striatum. The KYNA level in the MD samples was determined using the column-switching high-performance liquid chromatography system. KYNA levels in the MD samples increased by approximately twofold in rats that were administered D-Trp or L-Trp; this result suggests that just as L-Trp, D-Trp was also metabolized to KYNA in the striatum. Additionally, 30 min before the administration of D-Trp, rats were administered 3-methyl pyrazole-5-carboxylic acid (MPC) (50 mg/kg), which is a specific inhibitor of D-amino acid oxidase (DAAO). Pretreatment with MPC suppressed striatal KYNA production; this result suggests that DAAO, encoded by one of the susceptible genes for schizophrenia, may contribute to the production of KYNA from D-Trp in the striatum of rats.
犬尿酸（KYNA）是内源性 N-甲基-D-天冬氨酸和 α（7）烟碱型乙酰胆碱受体拮抗剂，是 L-色氨酸（Trp）代谢物之一。为了比较单独给予 L-Trp 和 D-Trp 后大鼠纹状体产生的 KYNA 水平，将大鼠腹腔内给予 L-Trp 和/或 D-Trp（100mg/kg），并在纹状体中植入微透析（MD）探针。使用柱切换高效液相色谱系统测定 MD 样品中的 KYNA 水平。给予 D-Trp 或 L-Trp 的大鼠 MD 样品中的 KYNA 水平增加了约两倍；这一结果表明，与 L-Trp 一样，D-Trp 也在纹状体中代谢为 KYNA。此外，在给予 D-Trp 之前 30 分钟，大鼠给予 3-甲基吡唑-5-羧酸（MPC）（50mg/kg），它是 D-氨基酸氧化酶（DAAO）的特异性抑制剂。MPC 预处理抑制纹状体 KYNA 的产生；这一结果表明，编码精神分裂症易感基因之一的 DAAO 可能有助于大鼠纹状体中 D-Trp 生成 KYNA。
