Stereoselective effect of kynurenine enantiomers on the excretion of serotonin and its metabolite in rat urine |
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Authors: | Tsukasa Sasaki Takeshi Fukushima Kazuhide Yamashita Toshimasa Toyo'oka |
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Institution: | 1. Division of Bio‐Analytical Chemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga‐ku, Shizuoka, Japan;2. Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi‐shi, Chiba, Japan |
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Abstract: | 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. Chirality, 2010. © 2009 Wiley‐Liss, Inc. |
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Keywords: | D‐kynurenine L‐kynurenine 5‐hydroxytryptamine 5‐hydroxyindole acetic acid rat urine |
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