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

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. Chirality, 2010. © 2010 Wiley‐Liss, Inc.