Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling.

Mina Ito, Taku Nagai, Hiroyuki Mizoguchi, Kosuke Sato, Minoru Hayase, Noboru Otsuka, Ayumi Fukakusa, Nozomi Kumagai, Hyoung Chun Kim, Toshitaka Nabeshima, Kazuhiro Takuma, Kiyofumi Yamada

研究成果: Article

12 引用 (Scopus)

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We have previously demonstrated that tissue plasminogen activator (tPA) plays an important role through the conversion of plasminogen to plasmin in the release of dopamine in the nucleus accumbens (NAc) evoked by depolarization or the systemic administration of drugs of abuse such as morphine and nicotine. In the present study, we examined the mechanisms by which drugs of abuse increase extracellular tPA activity in the NAc in vivo using in situ zymography. The dopamine D(1) receptor (D(1) R) agonist SKF38393, but not D(2) receptor agonist quinpirole, significantly increased extracellular tPA activity in the NAc. The effect of SKF38393 was blocked by pre-treatment with the dopamine D(1) R antagonist SCH23390. Microinjection of Rp-cAMPs, a protein kinase A inhibitor, into the NAc completely blocked the effect of SKF38393. Systemic administration of morphine and methamphetamine increased extracellular tPA activity in the NAc, and these effects were completely blocked by pre-treatment with SCH23390 and raclopride. The results suggest that activation of post-synaptic dopamine D(1) Rs in the NAc leads to an increase in extracellular tPA activity via protein kinase A signaling. Furthermore, dopamine D(2) receptors are also involved in the release of tPA induced by morphine and methamphetamine.

元の言語English
ページ(範囲)2589-2596
ページ数8
ジャーナルJournal of neurochemistry
103
発行部数6
出版物ステータスPublished - 01-12-2007
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

これを引用

Ito, M., Nagai, T., Mizoguchi, H., Sato, K., Hayase, M., Otsuka, N., Fukakusa, A., Kumagai, N., Kim, H. C., Nabeshima, T., Takuma, K., & Yamada, K. (2007). Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling. Journal of neurochemistry, 103(6), 2589-2596.