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.
Ishii
Kana
K
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba 274-8510, Japan.
Ogaya
Tadahiro
T
Song
Ziyu
Z
Iizuka
Hideaki
H
Fukushima
Takeshi
T
D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D003605:D-Amino-Acid Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000097:blood* / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007736:Kynurenic Acid / Q000097:blood* / Q000737:chemistry; D007737:Kynurenine / Q000097:blood* / Q000737:chemistry; D008297:Male; D009904:Optical Rotation; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014364:Tryptophan / Q000737:chemistry / Q000493:pharmacokinetics*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011720:Pyrazoles; D007737:Kynurenine; D014364:Tryptophan; D003605:D-Amino-Acid Oxidase; D007736:Kynurenic Acid; C005210:5-methylpyrazole-3-carboxylic acid