精神刺激薬によって差異的に調節されるセロトニントランスポーターの酸化と結合
1Department of Pharmacology and Center for Molecular Neuroscience, School of Medicine, Vanderbilt University, Nashville, TN 37232-6420, USA.
Science (New York, N.Y.)
|July 31, 1999
まとめ
精神薬は,SERTのような神経伝達物質のトランスポーターに影響します. リンガンド結合はトランスポーター活性に影響を与え,PKC依存経路を通じて薬剤の有効性と副作用に影響を与えます.
科学分野:
- 神経科学は神経科学である.
- 薬理学 薬理学とは
- 分子生物学は分子生物学である.
背景:
- 精神薬は神経伝達物質システムを調節する.
- タンパク質キナーゼC (PKC) を含むキナーゼ経路は,トランスポーター機能を調節する.
- トランスポーターのリン酸化と封じ込めは,重要な規制メカニズムです.
研究 の 目的:
- リガンド占有がタンパク質キナーゼC (PKC) に依存したセロトニントランスポーター (SERT) の調節にどのように影響するか調査する.
- SERTのリン酸化および封じ込めに対する輸送および非輸送リガンドの影響を明らかにする.
- 神経伝達物質の再吸収の活動依存的調節を理解するために.
主な方法:
- 様々なリガンド (セロトニン,アンフェタミン,コカイン,抗うつ薬) がSERTのリン酸化と封じ込めに及ぼす影響を研究した.
- 生化学的測定法を使用して,トランスポーター活動と調節イベントを測定しました.
- これらのリガンド誘発効果を媒介するPKCの役割を調査した.
主要な成果:
- リガンド占有量は,SERTのリン酸化と封じ込めに大きく影響した.
- 輸送されたリガンド (セロトニン,アンフェタミン) は,PKC依存型SERTのリン酸化を阻害した.
- 非輸送抗薬 (コカイン,抗うつ薬) は,SERTのリン酸化を許したが,セロトニンの効果を阻害した.
- また,セロトニンはPKCに依存するSERT連鎖を阻害した.
結論:
- 神経伝達物質のトランスポーター機能は,リガンド結合によって活性に依存した方法で調節されます.
- アンフェタミン,コカイン,抗うつ剤を含む薬物作用は,これまで認識されていないトランスポーター規制の影響を及ぼしています.
- 発見は,心理療法薬の有効性および副作用の基礎となる分子機構の洞察を提供します.
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