Changes in the plasma concentrations of D-kynurenine and kynurenic acid in rats after intraperitoneal administration of tryptophan enantiomers.

Kana Ishii, Tadahiro Ogaya, Ziyu Song, Hideaki Iizuka, Takeshi Fukushima

Index: Chirality 22 , 901-916, (2010)

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Abstract

An aqueous solution of enantiomerically pure tryptophan (Trp), namely, D-Trp or L-Trp (100 mg/kg), was administered intraperitoneally to male Sprague-Dawley rats. The time-course profiles of the rat plasma concentrations of D-kynurenine (KYN), L-KYN, and kynurenic acid (KYNA), which are metabolites of D- or L-Trp, were investigated using high-performance liquid chromatography (HPLC) systems that were reported in our previous study. The plasma D-KYN concentration increased after the administration of D-Trp, but this increase was not observed after the administration of L-Trp. The plasma L-KYN concentration increased after the administration of L-Trp, but no significant change was observed after the administration of D-Trp. The plasma KYNA concentration drastically increased in the case of rats administered D-Trp and those administered L-Trp. Additionally, an inhibitor of D-amino acid oxidase (DAAO), 5-methylpyrazole-3-carboxylic acid (MPC) (50 mg/kg), was administrated to the rats 30 min before the administration of D-Trp. The preadministration of MPC remarkably increased the D-KYN concentration and suppressed the production of KYNA. These results suggest that DAAO may contribute to the metabolism of D-KYN to KYNA in vivo.© 2010 Wiley-Liss, Inc.