title: Comparative study on kynurenic acid production in the rat striatum by tryptophan enantiomers: an in vivo microdialysis study.
abstract: 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.
authors: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors: Kana
authors: K
authors: Ishii
authors: Hideaki
authors: H
authors: Iizuka
authors: Tadahiro
authors: T
authors: Ogaya
authors: Ziyu
authors: Z
authors: Song
authors: Takeshi
authors: T
authors: Fukushima
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000378:metabolism*; D003605:D-Amino-Acid Oxidase / Q000737:chemistry*; D007736:Kynurenic Acid / Q000737:chemistry*; D007737:Kynurenine / Q000737:chemistry*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D008956:Models, Chemical; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry*
chemical_list: C492582:3-chloro-1-methyl-1H-pyrazole-5-carboxylic acid; D011720:Pyrazoles; D007737:Kynurenine; D014364:Tryptophan; D003605:D-Amino-Acid Oxidase; D007736:Kynurenic Acid