ヒト脳に内在するイソキノリンによるセロトニンの選択的放出の機序

1993 年度 実績報告書

• 研究課題/領域番号: 05260208
• 研究機関: 名古屋工業大学
• 研究代表者: 直井 信 名古屋工業大学, 工学部・保健体育教室, 教授 (50022786)
• キーワード: 神経伝達 / シナプス / インビボマイクロダイアリシス / セロトニン / イソキノリン / アルコール依存

研究概要

ヒト脳内でドパミンより生合成されるイソキノリン1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline(salsolinol)がラット脳でモノアミンを放出することをin vivo microdialysisを用い見い出した。イソキノリンの構造活性相関を検討したところカテコール核を有するイソキノリンはモノアミン遊離作用を示すが、持たない1,2,3,4-tetrahydoisoquinoline類は遊離を促進しないことがわかった。さらにカテコールイソキノリンのなかでもsalsolinolのみがセロトニンを選択的、強力に放出させることが明確となった。
salsolinolによるセロトニンの放出機序を検討した。セロトニンの放出は電気的神経伝達を伴わないこと、Naチャンネルを介した神経伝達機構も関与しないものであることがin vivo microdialysis法により証明された。脳内salsolinol濃度は飲酒により増加することが報告されており、このようなセロトニン放出作用はアルコールによる精神症状や依存の成立の生化学的機構と関連する可能性があると考えられる。
このためさらに研究を進めていきたい。

研究成果

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• [文献書誌] M.Naoi: "N-Methylated tetrahydroisoquinolines as dopaminergic neurotoxins" Advances in Neurology. 60. 212-217 (1993)
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• [文献書誌] 直井 信: "パーキンソン病の成因-神経毒の面から" 神経精神薬理. 14. 745-753 (1992)
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• [文献書誌] 丸山和佳子: "脳内カテコールアミンとインドールアミン代謝の相互作用" 神経化学. 32. 258-259 (1993)
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