Regulation of nicotine reward by the tissue plasminogen activator (tPA): plasmin system via proteinase-activated receptor 1

• Nagai Taku

  Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan

• Nabeshima Toshitaka

  Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Japan

• Yamada Kiyofumi

  Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan

書誌事項

タイトル別名

• Basic and Translational Research on Proteinase-Activated Receptors: Regulation of Nicotine Reward by the Tissue Plasminogen Activator (tPA) - Plasmin System via Proteinase-Activated Receptor 1

抄録

Nicotine, a primary component of tobacco, is one of the most abused drugs worldwide. Mesolimbic dopaminergic neurons mediate the rewarding effects of abused drugs, including nicotine. We show that the tissue plasminogen activator (tPA) – plasmin system regulates nicotine-induced reward and dopamine release in the nucleus accumbens (NAc) by activating proteinase-activated receptor 1 (PAR₁). Nicotine-induced conditioned place preference and dopamine release in the NAc are diminished in tPA knockout (tPA−/−) mice. The defect of nicotine-induced dopamine release in tPA−/− mice is reversed by microinjection of either exogenous tPA or plasmin into the NAc. Acute nicotine treatment increases tPA protein levels and promoted the release of tPA into the extracellular space. The expression of PAR₁ on dopaminergic neurons is evident and the activation of PAR₁ by plasmin is demonstrated by assaying GTP-γS binding. Finally, nicotine-induced conditioned place preference and dopamine release are diminished in PAR₁−/− mice. These findings suggest that targeting the tPA-plasmin–PAR₁ system would provide new therapeutic approaches for the treatment of nicotine dependence.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 108 (4), 408-414, 2008

  公益社団法人 日本薬理学会

キーワード

• dependence
• dopamine
• nicotine
• proteinase-activated receptor 1 (PAR₁)
• tissue plasminogen activator (tPA)

詳細情報

• CRID: 1390001205179668992
• NII論文ID: 10025732467
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.08r04fm
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 9751775
• Web Site: http://id.ndl.go.jp/bib/9751775
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9751775
• Web Site: https://search.jamas.or.jp/link/ui/2009144975
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可