Regulation of dopaminergic neural transmission by tyrosine hydroxylase protein at nerve terminals
-
- Sumi-Ichinose Chiho
- Department of Pharmacology, School of Medicine, Fujita Health University, Japan
-
- Ichinose Hiroshi
- Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Japan
-
- Ikemoto Kazuhisa
- Department of Pharmacology, School of Medicine, Fujita Health University, Japan
-
- Nomura Takahide
- Department of Pharmacology, School of Medicine, Fujita Health University, Japan
-
- Kondo Kazunao
- Department of Pharmacology, School of Medicine, Fujita Health University, Japan
書誌事項
- タイトル別名
-
- Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders: Regulation of Dopaminergic Neural Transmission by Tyrosine Hydroxylase Protein at Nerve Terminals
この論文をさがす
抄録
5R-L-Erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH). Recently, a type of dopa-responsive dystonia (DRD) (DYT5, Segawa’s disease) was revealed to be caused by dominant mutations of the gene encoding GTP cyclohydrolase I (GCHI), which is the rate-limiting enzyme of BH4 biosynthesis. In order to probe the role of BH4 in vivo, we established BH4-depleted mice by disrupting the 6-pyruvoyltetrahydropterin synthase (PTS) gene (Pts−/−) and rescued them by introducing human PTS cDNA under the control of the human dopamine β-hydroxylase (DBH) promoter (Pts−/−-DPS). The Pts−/−-DPS mice developed hyperphenylalaninemia. Interestingly, tyrosine hydroxylase protein was dramatically reduced in the dopaminergic nerve terminals of these mice, and they developed abnormal posture and motor disturbance. We propose that the biochemical and pathologic changes of Pts−/−-DPS mice are caused by mechanisms common to human DRD, and understanding these mechanisms could give us insight into other movement disorders.
収録刊行物
-
- Journal of Pharmacological Sciences
-
Journal of Pharmacological Sciences 114 (1), 17-24, 2010
公益社団法人 日本薬理学会
- Tweet
詳細情報
-
- CRID
- 1390282680156587136
-
- NII論文ID
- 10029889595
-
- NII書誌ID
- AA11806667
-
- ISSN
- 13478648
- 13478613
-
- NDL書誌ID
- 10823321
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可