STUDIES ON IN VIVO METABOLISM OF TRYPTOPHAN AND ITS METABOLITES USING COMBINED GAS CHROMATOGRAPHY / MASS SPECTROMETRY WITH USE OF STABLE ISOTOPE LABELED COMPOUNDS
| Project/Area Number |
61480245
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | National Institute of Neuroscience, NCNP |
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Principal Investigator |
HAYASHI Tokishi National Institute of Neuroscience, NCNP Section Chief, 神経研究所・診断研究部, 室長 (20082985)
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| Co-Investigator(Kenkyū-buntansha) |
MATAGA Nobuko National Institute of Neuroscience, NCNP Research Associate, 神経センター・神経研究所・診断研究部, 流動研究員
NARUSE Hiroshi National Institute of Neuroscience, NCNP Division Chief, 神経センター・神経研究所・診断研究部, 部長 (10159080)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | negative ion chemical ionization mass spectrometry / tracer experiment using stable isotope labeled compound / serotonin / tryptamine / 5-hydroxyindole-3-acetic acid / indole-acetic acid / kynurenine / キヌレニン / 負イオン化学 / イオン化質量分析法 / セロトニン / 血液脳関門 |
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| Research Abstract |
Investigations for development of sensitive GC/MS methods for the determination of tryptophan metabolites and application of the GC/MS methods with use of some deuterium labeled compounds to metabolic investigation were carried out and following results were obtained.
Highly sensitive GC/MS methods for the determination of 5-hydroxyindole-3- acetic acid, indole-3-acetic acid and kynurenine were developed and the methods were confirmed to be useful for metabolic investigations using deuterated tryptophan. L Tryptophan-3,3-d_2 was successfully used as a tracer for metabolic investigation of tryptophan to tryptamine, serotonin, indole-3-acetic acid and 5-hydroxyindole-3- acetic acid. However, the deuterated tryptophan was not usable as a tracer for metabolic investigation of tryptophan to kynurenine because of D-H exchange reaction. L-Tryptophan-2,3-^<13>C_2 was therefore synthesized for simultaneous metabolic studies of tryptophan to its metabolites described above. By GC/MS methods with use of stable isotope labeled compounds, some experiments were carried out to investigate where urinary serotonin and tryptamine were synthesized. Concerning serotonin synthesis, there were no organs except the brain which have high molar ratio of serotonin-d_2 to endogenous one as that in urine. Therefore, it could be postulated that serotonin-d_2 in urine might reflect the serotonin synthesis in the brain. In the case of tryptamine, tryptamine-d_2 in urine could be derived form liver or other peripheral oragans. It is believed that serotonin could not pass through the blood brain barrier. However, the data supporting the suggestion have not been clearly confirmed. Therefore, the penetration of serotonin was investigated. And it was confirmed that serotonin could penetrate through blood brain barrier. Tacer experiments with use of tryptophan-d_2 were carried out in four autistic children and abnormal excretion pattern of serotonin-d_2 was found.
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Report
(2 results)
Research Products
(11 results)
