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Alteration of kynurenic acid concentration in rat plasma following optically pure kynurenine administration: A comparative study between enantiomers
Author(s) -
Fukushima Takeshi,
Sone Yukiko,
Mitsuhashi Shogo,
Tomiya Masayuki,
Toyo'oka Toshimasa
Publication year - 2009
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20620
Subject(s) - kynurenic acid , chemistry , kynurenine , metabolite , enantiomer , tryptophan , antagonist , nicotinic agonist , pharmacology , amino acid , biochemistry , receptor , stereochemistry , medicine
L ‐Kynurenine (KYN), a tryptophan metabolite, is metabolized to kynurenic acid (KYNA), which is an antagonist of N ‐methyl‐ D ‐aspartate and α7 nicotinic acetylcholine receptors, by kynurenine aminotransferase (KAT) I and KAT II. In this study, optically pure KYN, namely L ‐KYN or D ‐KYN, was administered intraperitoneally to male Sprague‐Dawley rats (16.3 μmol kg −1 ), and the change in plasma KYNA was investigated by using column‐switching high‐performance liquid chromatography (HPLC) with fluorescence detection. Unexpectedly, no remarkable alteration in the plasma KYNA was observed when a natural isomer, L ‐KYN, was administered, whereas plasma KYNA concentration was unequivocally increased when an unnatural isomer, D ‐KYN, was administered. Serum protein bindings of L ‐KYN and D ‐KYN were also studied, and the protein binding of L ‐KYN (∼65%) in rat serum was larger than that of D ‐KYN (∼12%), suggesting that D ‐KYN may be easily incorporated and metabolized in tissues during blood circulation to generate KYNA in mammals. In addition, the increase in plasma KYNA by the administration of D ‐KYN was suppressed in rats pretreated with a selective inhibitor of D ‐amino acid oxidase (DAAO), 5‐methylpyrazole‐3‐carboxylic acid (80 mg/kg). These results suggest that DAAO might be responsible for the production of KYNA from D ‐KYN in vivo. Chirality, 2009. © 2008 Wiley‐Liss, Inc.