| Project/Area Number |
11680760
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kyoto prefectural University of Medicine |
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Principal Investigator |
HASHIMOTO Tsuneichi Kyoto prefectural University of Medicine, Department of Pharmacology, lecturer, 医学部, 講師 (00172867)
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| Co-Investigator(Kenkyū-buntansha) |
IWATA Kazumi Kyoto prefectural University of Medicine, Department of Pharmacology, Assistant, 医学部, 助手 (60305571)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | dopamine / PC12 cell / Parkinsonism / DOPALD / ドパミン / アルデヒド / 神経伝達物質遊離 |
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| Research Abstract |
An endogenous aldehyde, 3,4-dihydoxyphenylacetaldehyde (DOPALD) is generated from dopamine (DA) by monoamine oxidase (MAO) as the initial metabolite of DA.Similar to a dopaminergic neurotoxin such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), DOPALD is thought to be one of the candidate substances that provoke idiopathic Parkinson's disease. In fact, DOPALD has been detected in the substantia nigra of parkinsonian patients but not in the control subjects. In the present study, we set out to examine the direct effects of DOPALD on DA release using PC12 cells. DOPALD at concentration 1-100 μM elicited DA release from PC 12 cells in a dose dependent manner. LDH leakage from PC12 cells did not affect by the treatment of DOPALD up to 10μm. Addition of 4-hydroxy-2-nonenal (1-100μM), one of the endogenous aldehydes generated during lipid peroxidation, did not affect the DA release from the PC12 cells. No significant effect of DOPALD (up to 10μM) was depicted on [3H]DA (2nM) uptake into the cells. Although high potassium (56mM)-induced DA release from PC12 cells was dependent on extracellular Ca^<2+> concentration and was blocked by nifedipine, L-type Ca channel antagonist, DOPALD-induced DA release did not depend on extracellular Ca2+ concentration and was not blocked by nifedipine. These data indicate the specificity of an endogenous aldehyde DOPALD on DA release from PC12 cells, and DOPALD-induced DA release from PC12 cells was caused by Ca^<2+>-independent manner.
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