Won J S, Im Y B, Kim Y H, Song D K, Huh S O, Suh H W
Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do, 200-702, South Korea.
Brain Res Mol Brain Res. 1998 May;56(1-2):76-83. doi: 10.1016/s0169-328x(98)00031-x.
The effect of L-arginine (L-ARG), a nitric oxide donor, or Nomega-nitro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, on the regulation of kainic acid (KA)-induced proenkephalin (proENK) and prodynorphin (proDYN) mRNA expressions in rat hippocampus was studied. The proENK and proDYN mRNA levels were markedly increased 6 h after KA (10 mg/kg, i.p.) administration. The elevations of both proENK and proDYN mRNA levels induced by KA was effectively inhibited by pre-administration of L-ARG (400 mg/kg, i.p.), but was not affected by pre-treatment with L-NAME (200 mg/kg, i.p.). The blockade of KA-induced proENK and proDYN mRNA levels by the pre-treatment with L-ARG was well correlated with proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, JunD, JunB, and c-Jun, as well as AP-1 and ENKCRE-2 DNA binding activities. The pre-administration with L-NAME further increased KA-induced c-jun and c-fos mRNA levels in addition to their protein product levels, although the pre-treatment with L-NAME did not affect KA-induced FosB, Fra-2, JunB, and JunD protein levels at 6 h after treatment. In addition, the pre-administration with L-NAME further increased the KA-induced AP-1 and ENKCRE-2 DNA binding activities. Our results suggest that L-ARG plays an important role in inhibiting KA-induced proENK or proDYN mRNA expression, and its inhibitory action may be mediated through reducing the proto-oncoprotein levels, such as c-Fos, Fra-2, FosB, c-Jun, JunD, and JunB. In addition, L-NAME potentiated the c-Fos or c-Jun gene expression, as well as AP-1 or ENKCRE-2 DNA binding activity. However, these increases did not show the potentiative effect on KA-induced increases of proENK and proDYN mRNA level.
研究了一氧化氮供体L-精氨酸（L-ARG）或一氧化氮合酶抑制剂Nω-硝基-L-精氨酸（L-NAME）对大鼠海马中 kainic 酸（KA）诱导的前脑啡肽原（proENK）和前强啡肽原（proDYN）mRNA 表达调控的影响。腹腔注射KA（10 mg/kg）6小时后，proENK和proDYN mRNA水平显著升高。KA诱导的proENK和proDYN mRNA水平升高可被预先腹腔注射L-ARG（400 mg/kg）有效抑制，但不受预先腹腔注射L-NAME（200 mg/kg）的影响。预先用L-ARG处理对KA诱导的proENK和proDYN mRNA水平的阻断与原癌蛋白水平（如c-Fos、Fra-2、FosB、JunD、JunB和c-Jun）以及AP-1和ENKCRE-2 DNA结合活性密切相关。预先注射L-NAME除了增加KA诱导的c-jun和c-fos mRNA水平及其蛋白产物水平外，还进一步增加了KA诱导的AP-1和ENKCRE-2 DNA结合活性，尽管在处理后6小时，预先注射L-NAME对KA诱导的FosB、Fra-2、JunB和JunD蛋白水平没有影响。此外，预先注射L-NAME进一步增加了KA诱导的AP-1和ENKCRE-2 DNA结合活性。我们的结果表明，L-ARG在抑制KA诱导的proENK或proDYN mRNA表达中起重要作用，其抑制作用可能通过降低原癌蛋白水平（如c-Fos、Fra-2、FosB、c-Jun、JunD和JunB）来介导。此外，L-NAME增强了c-Fos或c-Jun基因表达以及AP-1或ENKCRE-2 DNA结合活性。然而，这些增加并未显示出对KA诱导的proENK和proDYN mRNA水平升高的增强作用。
