Stereoselective effect of kynurenine enantiomers on the excretion of serotonin and its metabolite in rat urine.
A solution of optically pure kynurenine (KYN), i.e., D-KYN or L-KYN, was administered intravenously to male Sprague-Dawley rats (10 mg kg(-1) ml(-1)). The time-course of changes in the concentrations of urinary monoamines and their metabolites such as 5-hydroxytryptamine (5-HT), 5-hydroxyindole acetic acid (5-HIAA), dopamine, and 3-methoxytyramine were investigated by reversed-phase high-performance liquid chromatography with electrochemical detection after precolumn derivatization with (2R)-2,5-dioxopyrrolidin-1-yl-2,5,7,8-tetramethyl-6-(tetrahydro-2H-pyran-2-yloxy)chroman-2-carboxylate (NPCA). We observed a stereoselective difference in the effects of the KYN enantiomers. Only D-KYN, not L-KYN, caused a significant increase in urinary 5-HT levels within 30 min after its administration. With regard to the metabolites, urinary 3-MT level was increased by D-KYN administration. On the other hand, no significant change in the DA level was observed after administration of either D-KYN or L-KYN. These results suggest that D-KYN could affect the activity of neuroactive amines, especially 5-HT, in vivo.
Sasaki
Tsukasa
T
Division of Bio-Analytical Chemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
Fukushima
Takeshi
T
Yamashita
Kazuhide
K
Toyo'oka
Toshimasa
T
D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000031:analogs & derivatives / Q000235:genetics*; D006897:Hydroxyindoleacetic Acid / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism; D007737:Kynurenine / Q000494:pharmacology*; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D017208:Rats, Wistar; D012701:Serotonin / Q000652:urine*; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D002264:Carboxylic Acids; D007211:Indoles; C026785:5-hydroxyindole; D012701:Serotonin; D007737:Kynurenine; D006897:Hydroxyindoleacetic Acid; C001746:3-methoxytyramine; D004298:Dopamine