Biochemical and behavioral profiles of phosphodiesterase inhibition in dopaminergic neurotransmission
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- Nishi Akinori
- Department of Pharmacology, Kurume University School of Medicine, Japan Japan Science of Technology Agency, CREST, Japan
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- Snyder Gretchen L.
- Intra-Cellular Therapies, Inc., USA
書誌事項
- タイトル別名
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- Advanced Research on Dopamine Signaling to Develop Drugs for the Treatment of Mental Disorders: Biochemical and Behavioral Profiles of Phosphodiesterase Inhibition in Dopaminergic Neurotransmission
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説明
Dopamine plays a central role in the regulation of psychomotor functions. The effect of dopamine is largely mediated through the cAMP/PKA signaling cascade and therefore controlled by phosphodiesterases (PDEs). Multiple PDEs with different substrate specificities and subcellular localization are expressed in the striatum, and the functional roles of PDE10A, PDE4, and PDE1B are extensively studied. Biochemical and behavioral profiles of PDE inhibition by selective inhibitors and/or genetic deletion related to dopaminergic neurotransmission are compared among those PDEs. The inhibition of PDE up-regulates cAMP/PKA signaling in three neuronal subtypes, resulting in the stimulation of dopamine synthesis at dopaminergic terminals, the inhibition of dopamine D2–receptor signaling in striatopallidal neurons, and the stimulation of dopamine D1–receptor signaling in striatonigral neurons. Predominant roles of PDE families or isoforms are implicated in each neuronal subtype: PDE4 at dopaminergic terminals, PDE10A and PDE4 in striatopallidal neurons, and PDE1B in striatonigral neurons. PDE10A and PDE4 inhibition may exhibit D2 antagonist–like, antipsychotic effects, whereas PDE1B inhibition may exhibit D1 agonist–like effects in the striatum. Development of PDE isoform–specific inhibitors is essential for better understanding of the function of each PDE isoform and treatment of neuropsychiatric disorders.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 114 (1), 6-16, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205179873920
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- NII論文ID
- 10029889521
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10823311
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可