Activation of post‐synaptic dopamine D1 receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling
Activation of post‐synaptic dopamine D1 receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling
复制标题
DOI：
10.1111/j.1471-4159.2007.04946.x
复制
发表时间：
2007-12
影响因子：
4.7
通讯作者：
Mina Ito;T. Nagai;H. Mizoguchi;Kosuke Sato;M. Hayase;N. Otsuka;Ayumi Fukakusa;Nozomi Kumagai;Hyoung‐Chun Kim;T. Nabeshima;K. Takuma;Kiyofumi Yamada
中科院分区：
文献类型：
--
作者：
Mina Ito;T. Nagai;H. Mizoguchi;Kosuke Sato;M. Hayase;N. Otsuka;Ayumi Fukakusa;Nozomi Kumagai;Hyoung‐Chun Kim;T. Nabeshima;K. Takuma;Kiyofumi Yamada
我们以前已经证明，组织型纤溶酶原激活剂（tPA）通过纤溶酶原转化为纤溶酶在多巴胺的释放中起着重要的作用，在去极化或全身给药的药物滥用，如吗啡和尼古丁引起的丘脑核（NAc）。在本研究中，我们研究的机制，滥用药物增加细胞外tPA活性的NAC在体内使用原位酶谱。多巴胺D1受体（D1 R）激动剂SKF 38393，而不是D2受体激动剂quinpirole，显着增加细胞外tPA活性的NAc。SKF 38393的作用通过多巴胺D1 R拮抗剂SCH 23390的预处理来阻断。将蛋白激酶A抑制剂Rp-cAMPs微量注射到NAc中完全阻断了SKF 38393的作用。吗啡和甲基苯丙胺的全身给药增加了NAc的细胞外tPA活性，这些作用被SCH 23390和雷氯必利的预处理完全阻断。结果表明，NAc中突触后多巴胺D1 R的激活通过蛋白激酶A信号传导导致细胞外tPA活性增加。此外，多巴胺D2受体也参与吗啡和甲基苯丙胺诱导的tPA释放。
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 D1 receptor (D1R) agonist SKF38393, but not D2 receptor agonist quinpirole, significantly increased extracellular tPA activity in the NAc. The effect of SKF38393 was blocked by pre‐treatment with the dopamine D1R 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 D1Rs in the NAc leads to an increase in extracellular tPA activity via protein kinase A signaling. Furthermore, dopamine D2 receptors are also involved in the release of tPA induced by morphine and methamphetamine.