| Project/Area Number |
10470495
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Hiroshima University |
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Principal Investigator |
OHTA Shigeru Hiroshima University, Faculty of Medicine, Professor, 医学部, 教授 (60160503)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIHARA Kazumi Hiroshima University, Faculty of Medicine, Research Associate, 医学部, 教務員 (20271067)
KITAMURA Shigeyuki Hiroshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (40136057)
YOSHIHARA Shinichi Hiroshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00037607)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Parkinson's disease / tetrahydroisoquinoline / Parkinson's disease cpreventing substance / dopaminergic neuron / Parkinson's disease causing substance / cell culture |
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| Research Abstract |
1, 2, 3, 4-Tetrahydroisoqpinoline (TIQ) derivatives, which chemically resemble MPTP, exist in mammals and have been proposed as candidates for endogenous parkinsonogenic compounds.
It was recently reported 1-benzyl-1, 2, 3, 4-tetrahydroisoqpinoline (1BnTIQ) is present in human cerebrospinal fluid and mouse brain, and proposed that 1BnTIQ is biosynthesized from 2-phenylethylamine and phenylacetaldehyde which is a metabolite of 2-pherrylethylamine generated by monoanrine oxidase-type B. The 1BnTIQ content in cerebrospinal fluid of patients with PD is higher than that of patients with other neurological diseases. Further, repeated administration of this compound induced parkinsonism in the monkey and mouse. 1BnTIQ inhibited dopamine uptake through dopamine transporter (DAT) expressed in HEK293 cells, suggesting that 1BnTIQ is uptaken through DAT as 1-methyl-4-phenylpyridinium ion, which is an active metabolite of dopaminergic neurotoxin, MPTP. We also reported that various tetrahydroisoquinoline derivatives including 1BnTIQ inhibited mitochondrial respiration and the electron transfer complexes.
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