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Microdialysis with radiometric monitoring of L-[beta-11C]DOPA metabolites in rat striatum and plasma
https://repo.qst.go.jp/records/70227
https://repo.qst.go.jp/records/70227b51dbf80-9cb4-4b2a-aa1c-a4f1363d84d5
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2010-09-13 | |||||
タイトル | ||||||
タイトル | Microdialysis with radiometric monitoring of L-[beta-11C]DOPA metabolites in rat striatum and plasma | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Okada, Maki
× Okada, Maki× Nakao, Ryuji× Hosoi, Rie× Zhang, Ming-Rong× Fukumura, Toshimitsu× Suzuki, Kazutoshi× Inoue, Osamu× 岡田 真希× 中尾 隆士× 細井 理恵× 張 明栄× 福村 利光× 鈴木 和年× 井上 修 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | The catecholamine, dopamine (DA), is synthesized from 3,4-dihydroxy-L-phenylalanine (L-DOPA) by aromatic L-amino acid decarboxylase (AADC). DA metabolism is regulated by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). To measure dopaminergic metabolism, we used microdialysis with radiometric detection to monitor L-[beta-11C]DOPA metabolites in the extracellular space of the rat striatum and plasma. We also evaluated the effects of AADC, MAO, and COMT inhibitors on striatal metabolite profiles. L-[beta-11C]DOPA and its radioactive metabolites, [11C]3,4-dihydroxyphenylacetic acid ([11C]DOPAC), [11C]homovanillic acid ([11C]HVA), L-3-O-methyl-[11C]DOPA ([11C]3-OMD) and [11C]3-methoxytyramine ([11C]3-MT) were detected, however [11C]DA was not detected in striatal dialysate following intravenous injection of L-[beta-11C]DOPA. The major early species measured after administration of L-[beta-11C]DOPA were [11C]DOPAC and [11C]HVA in a 1:1 ratio, which shifted toward [11C]HVA with time. An AADC inhibitor increased the uptake of L-[beta-11C]DOPA and [11C]3-OMD and delayed the accumulation of [11C]DOPAC and [11C]HVA. With MAO inhibition, about 80% of total radioactivity was derived from [11C]3-MT. The COMT inhibitor increased [11C]DOPAC and decreased [11C]HVA. L-[beta-11C]DOPA and [11C]3-OMD were detected and then achieved equilibrium in plasma with AADC inhibitor. On the other hand, [11C]3-OMD levels in striatal dialysate decreased significantly following intrastriatal administration of L-[beta-11C]DOPA. These results suggest that [11C]3-OMD in striatal dialysate was generated mostly in peripheral tissue and penetrate into brain. Our results reflect the complicated L-DOPA metabolic pathway, suggesting that this method could improve the understanding of the information obtained from an L-[beta-11C]DOPA PET study or provide an index of dopaminergic metabolism-related neuropsychiatric disorders and evaluation of drug therapies for treatment of the disorder. |
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会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | 2010 World Molecular Imaging Congress | |||||
発表年月日 | ||||||
日付 | 2010-09-11 | |||||
日付タイプ | Issued |