Ito Mina, Nagai Taku, Kamei Hiroyuki, Nakamichi Noritaka, Nabeshima Toshitaka, Takuma Kazuhiro, Yamada Kiyofumi
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Mol Pharmacol. 2006 Nov;70(5):1720-5. doi: 10.1124/mol.106.022467. Epub 2006 Aug 14.
Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin. In the present study, we investigated the role of the tPA-plasmin system in depolarization-evoked dopamine (DA) and acetylcholine (ACh) release in the nucleus accumbens (NAc) and hippocampus, respectively, of mice, by using in vivo microdialysis. Microinjection of either tPA or plasmin significantly potentiated 40 mM KCl-induced DA release without affecting basal DA levels. In contrast, plasminogen activator inhibitor-1 dose-dependently reduced 60 mM KCl-induced DA release. The 60 mM KCl-evoked DA release in the NAc was markedly diminished in tPA-deficient (tPA-/-) mice compared with wild-type mice, although basal DA levels did not differ between the two groups. Microinjections of either exogenous tPA (100 ng) or plasmin (100 ng) into the NAc of tPA-/-mice restored 60 mM KCl-induced DA release, as observed in wild-type mice. In contrast, there was no difference in either basal or 60 mM KCl-induced ACh release in the hippocampus between wild-type and tPA-/-mice. Our findings suggest that the tPA-plasmin system is involved in the regulation of depolarization-evoked DA release in the NAc.
组织型纤溶酶原激活物（tPA）是一种丝氨酸蛋白酶，可催化纤溶酶原转化为纤溶酶。在本研究中，我们通过体内微透析分别研究了tPA-纤溶酶系统在小鼠伏隔核（NAc）和海马体中去极化诱发的多巴胺（DA）和乙酰胆碱（ACh）释放中的作用。微量注射tPA或纤溶酶均可显著增强40 mM氯化钾诱导的DA释放，而不影响基础DA水平。相反，纤溶酶原激活物抑制剂-1剂量依赖性地降低了60 mM氯化钾诱导的DA释放。与野生型小鼠相比，tPA缺陷型（tPA-/-）小鼠伏隔核中60 mM氯化钾诱发的DA释放明显减少，尽管两组之间的基础DA水平没有差异。向tPA-/-小鼠的伏隔核中微量注射外源性tPA（100 ng）或纤溶酶（100 ng）均可恢复60 mM氯化钾诱导的DA释放，这与野生型小鼠中观察到的情况相同。相反，野生型和tPA-/-小鼠海马体中基础或60 mM氯化钾诱导的ACh释放均无差异。我们的研究结果表明，tPA-纤溶酶系统参与了伏隔核中去极化诱发的DA释放的调节。
