2002 Fiscal Year Final Research Report Summary
Regulation of dopamine transporter function and its role in neuronal diseases - Regulation by arachidonic acid.
| Project/Area Number |
13470392
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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 |
Functional basic dentistry
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
DOHI Toshihiro Hiroshima University Graduate School of Biomedical Sciences, Dental Pharmacology, Professor, 大学院・医歯薬学総合研究科, 教授 (00034182)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAHARA Michio Hiroshima University Graduate School of Biomedical Sciences, Dental Anesthesiology, Professor, 大学院・医歯薬学総合研究科, 教授 (30034094)
MORITA Katsuya Hiroshima University Graduate School of Biomedical Sciences, Dental Pharmacology, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (10116684)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Arachidonoc acid / Monoamine transporter / MPP+ / Indomethacin / Ibuprofen / Dopamine / L-DOPA / Desipramine |
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| Research Abstract |
Regulation of dopamine transporter (DAT) and its role in the regulation of neuronal activities and the development of neuronal toxicities were studied in various cell systems expressing DAT.
1. MPP^+ induced cell death in COS cells expressing rat DAT cDNA (COS/DAT) and in PC 12 cells.
2. Treatment of PC 12 cells with reserpine enhanced MPP^+-induced cell death and α-methyl-p-tyrosine did not affect the cell death.
3. Treatment of PC12 cells with indomethacin and ibuprofen enhanced MPP^+-induced cell death but aspirin and NS-398, an specific inhibitor of COX-2 did not affect the cell death.
4. Ligands for PPARγ produced cell death with high concentrations.
5. Arachidonic acid enhanced dopamine uptake in BSA free-medium.
6. L-DOPA enhanced dopamine uptake in COS/DAT. The effect of L-DOPA was not inhibited by BCH, an inhibitor of L-system.
7. L-DOPA enhanced dopamine uptake at low concentrations and reduced the uptake at high concentrations in SK-N-SH cells and PC 12 cells.
8. L-DOPA inhibited dopamine uptake in rat striatum synaptosomes and the effect was blocked by BCH, and the inhibitors of aromatic amino acid decarboxylase.
9. Local anesthetics exhibiting inhibitory action on monoamine transporter produced kindling convulsions by repeated administrations in mice. Repeated administration of norepinephrine transporter inhibitors enhanced lidocaine-induced convulsions and attenuated cocaine-induced convulsions. SSRI enhanced lidocaine-convulsions in acute treatment but little effect by the chronic treatment. These results revealed a part of regulation of dopamine transport function.
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