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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2589-2596
Number of pages8
JournalJournal of Neurochemistry
Volume103
Issue number6
Publication statusPublished - 01-12-2007
Externally publishedYes

Fingerprint

Dopamine Receptors
Nucleus Accumbens
Tissue Plasminogen Activator
Dopamine
Chemical activation
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
Morphine
Methamphetamine
Street Drugs
Cyclic AMP-Dependent Protein Kinases
Raclopride
Quinpirole
Plasminogen
Fibrinolysin
Depolarization
Microinjections
Protein Kinase Inhibitors
Nicotine
Therapeutics

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Ito, M., Nagai, T., Mizoguchi, H., Sato, K., Hayase, M., Otsuka, N., ... 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.
Ito, Mina ; Nagai, Taku ; Mizoguchi, Hiroyuki ; Sato, Kosuke ; Hayase, Minoru ; Otsuka, Noboru ; Fukakusa, Ayumi ; Kumagai, Nozomi ; Kim, Hyoung Chun ; Nabeshima, Toshitaka ; Takuma, Kazuhiro ; Yamada, Kiyofumi. / Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling. In: Journal of Neurochemistry. 2007 ; Vol. 103, No. 6. pp. 2589-2596.
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abstract = "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.",
author = "Mina Ito and Taku Nagai and Hiroyuki Mizoguchi and Kosuke Sato and Minoru Hayase and Noboru Otsuka and Ayumi Fukakusa and Nozomi Kumagai and Kim, {Hyoung Chun} and Toshitaka Nabeshima and Kazuhiro Takuma and Kiyofumi Yamada",
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Ito, M, Nagai, T, Mizoguchi, H, Sato, K, Hayase, M, Otsuka, N, Fukakusa, A, Kumagai, N, Kim, HC, 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, vol. 103, no. 6, pp. 2589-2596.

Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling. / Ito, Mina; Nagai, Taku; Mizoguchi, Hiroyuki; Sato, Kosuke; Hayase, Minoru; Otsuka, Noboru; Fukakusa, Ayumi; Kumagai, Nozomi; Kim, Hyoung Chun; Nabeshima, Toshitaka; Takuma, Kazuhiro; Yamada, Kiyofumi.

In: Journal of Neurochemistry, Vol. 103, No. 6, 01.12.2007, p. 2589-2596.

Research output: Contribution to journalArticle

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T1 - Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling.

AU - Ito, Mina

AU - Nagai, Taku

AU - Mizoguchi, Hiroyuki

AU - Sato, Kosuke

AU - Hayase, Minoru

AU - Otsuka, Noboru

AU - Fukakusa, Ayumi

AU - Kumagai, Nozomi

AU - Kim, Hyoung Chun

AU - Nabeshima, Toshitaka

AU - Takuma, Kazuhiro

AU - Yamada, Kiyofumi

PY - 2007/12/1

Y1 - 2007/12/1

N2 - 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.

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