Kim H C, Suh J H, Won J S, Jhoo W K, Song D K, Kim Y H, Wie M B, Suh H W
College of Pharmacy, Kangwon National University, Kangwon-Do, South Korea.
Brain Res. 1998 Jan 26;782(1-2):337-42. doi: 10.1016/s0006-8993(97)01401-7.
To determine the possible role of cyclooxygenase/lipoxygenase pathway in the regulation of proenkephalin (proENK) and prodynorphin (proDYN) gene expression induced by kainic acid (KA) in rat hippocampus, the effects of esculetin, aspirin, or phenidone on the seizure activity, proENK and proDYN mRNA levels, and the level of fos-related antigene (Fra) protein induced by KA in rat hippocampus were studied. Esculetin (5 mg/kg), aspirin (15 mg/kg), or phenidone (50 mg/kg) was administered orally five times every 12 h before the injection of KA (10 mg/kg, i.p.). Seizure activity induced by KA was significantly attenuated by phenidone. However, neither esculetin nor aspirin affected KA-induced seizure activity. The proENK and proDYN mRNA levels were markedly increased 4 and 24 h after KA administration. The elevations of both proENK and proDYN mRNA levels induced by KA were inhibited by pre-administration with phenidone, but not with esculetin and aspirin. ProENK-like protein level increased by KA administration was also inhibited by pre-administration with phenidone, but not with esculetin and aspirin. The increases of proENK and proDYN mRNA levels induced by KA were well correlated with the increases of Fra protein level. Additionally, the induction of Fra protein was inhibited by pre-administration with phenidone, but not with esculetin and aspirin. The results suggest that blockade of both cyclooxygenase and lipoxygenase pathways appears to be responsible for increases of proENK and proDYN mRNA levels induced by KA via inhibiting the induction of Fra protein in rat hippocampus.
为了确定环氧化酶/脂氧合酶途径在调节海藻酸（KA）诱导的大鼠海马中前脑啡肽原（proENK）和前强啡肽原（proDYN）基因表达中的可能作用，研究了七叶亭、阿司匹林或非那吡啶对KA诱导的大鼠海马癫痫活动、proENK和proDYN mRNA水平以及Fos相关抗原（Fra）蛋白水平的影响。在注射KA（10mg/kg，腹腔注射）前，每12小时口服给予七叶亭（5mg/kg）、阿司匹林（15mg/kg）或非那吡啶（50mg/kg）5次。非那吡啶可显著减轻KA诱导的癫痫活动。然而，七叶亭和阿司匹林均不影响KA诱导的癫痫活动。KA给药后4小时和24小时，proENK和proDYN mRNA水平显著升高。预先给予非那吡啶可抑制KA诱导的proENK和proDYN mRNA水平升高，但七叶亭和阿司匹林则无此作用。预先给予非那吡啶也可抑制KA给药后proENK样蛋白水平的升高，但七叶亭和阿司匹林则无此作用。KA诱导的proENK和proDYN mRNA水平升高与Fra蛋白水平升高密切相关。此外，预先给予非那吡啶可抑制Fra蛋白的诱导，但七叶亭和阿司匹林则无此作用。结果表明，环氧化酶和脂氧合酶途径的阻断似乎是通过抑制大鼠海马中Fra蛋白的诱导而导致KA诱导的proENK和proDYN mRNA水平升高的原因。
