| Project/Area Number |
10470026
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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 |
General pharmacology
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| Research Institution | Yokohama City University |
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Principal Investigator |
GOSHIMA Yoshio (1999) Yokohama City University School of Medicine Professor, 医学部, 教授 (00153750)
三須 良實 (1998) 横浜市立大学, 医学部, 教授 (10025687)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Yukio Yokohama City University School of Medicine Professor, 医学部, 助手 (10295511)
MIYAMAE Takeaki Yokohama City University School of Medicine Research associate, 医学部, 助手 (00239435)
古川 信也 横浜市立大学, 医学部, 助手 (90285114)
五嶋 良郎 横浜市立大学, 医学部, 助教授 (00153750)
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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 |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 1998: ¥8,900,000 (Direct Cost: ¥8,900,000)
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| Keywords | L-DOPA / nucleus tractus solitarii / baroreceptor reflex / striatum / ischemia / neuronal cell death / transporter / hippocampus / 圧受容器情報伝達物質ドーパ / 孤束核-尾側腹外側延髄ドーパ性投射 / 孤束核単離細胞 / 高電位活性化Ca^<2+>チャネル電流促進 / ドーパトランスポーター / 4血管閉塞脳虚血 / 神経細胞死因子ドーパ / 脳虚血グルタミン酸誘発上流因子内因性ドーパ |
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| Research Abstract |
[I] Function of L-DOPA in baroreceptor reflex:
[1] (1) Electrolytic lesions of the right nucleus tractus solitarii selectively decrease by 45 % the tissue content of L-DOPA in the dissected ipsilateral caudal ventrolateral medulla.
(2) Intermittent stimulation of the right aortic depressor nerve repetitively and constantly causes L-DOPA release, hypotension and bradycardia.
(3) Baroreceptor activation selectively evokes L-DOPA. This L-DOPA release is suppressed by acute lesion in the ipsilateral nucleus tractus solitarii.
[2] In a single cell neuron isolated from nucleus tractus solitarii, L-DOPA 0.1 to 1 mM augments HVA Ca2+ current with the maximal effect of 50 % over the control current. The effect is blocked by L-DOPA methyl ester, a competitive L-DOPA antagonist.
[II] Identification of L-DOPA as a casual factor for delayed neuronal cell death induced by brain ischemia: Ten-min transient ischemia due to four vessel occlusion increases extracellular L-DOPA, dopamine and glutamate during rat striatal microdialysis, and elicits neuronal cell death. Intrastriatal perfusion of 10-100 nM L-DOPA cyclohexyl ester, a competitive DOPA antagonist, 10 min before ischemia, concentration-dependently decreases glutamate release without modification of dopamine release by ischemia, and protects neurons from cell death.
[III] L-DOPA transporter:
(1) In Xenopus laevis oocytes, injected with polyA+ RNA from rabbit intestinal epithelium, the transport activity for L-[14C]DOPA with a high affinity is observed. This uptake was partially Na+-dependent but Cl- -independent. L-Tyrosine, -phenylalanine, -leucine and E〜lysine inhibit this transport activity. Coinjection of an antisence cRNA, as well as oligonucleotide complementary to rabbit rBAT cDNA almost completely inhibited the uptake of L-[14C]DOPA in the oocytes. rBAT is thus responsible for the L-[14C]DOPA uptake activity.
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