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清醒大鼠海马和纹状体对外源性L-精氨酸产生一氧化氮的不同反应:一项微透析研究。

Different response to exogenous L-arginine in nitric oxide production between hippocampus and striatum of conscious rats: a microdialysis study.

作者信息

Hara Shuichi, Mukai Toshiji, Kurosaki Kunihiko, Mizukami Hajime, Kuriiwa Fumi, Endo Takahiko

机构信息

Department of Forensic Medicine, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.

出版信息

Neurosci Lett. 2004 Aug 19;366(3):302-7. doi: 10.1016/j.neulet.2004.05.055.

Abstract

We previously showed that systemic administration of a nitric oxide (NO) precursor, L-arginine (L-Arg), failed to reverse suppression by NO synthase (NOS) inhibitors of chemically induced shaking behavior in rats, leading to the hypothesis that exogenous L-Arg might be non-uniformly supplied to brain regions susceptible to NOS inhibitors. In the present study, therefore, we examined the effect of exogenous L-Arg on the extracellular levels of the oxidative nitric oxide (NO) products, nitrite (NO2-) and nitrate (NO3-), in two different brain regions, the hippocampus and the striatum, of conscious rats by means of in vivo brain microdialysis. The basal NO2- levels in the two brain regions were comparable, while the NO3- level was significantly lower in the hippocampus than the striatum. The addition of 10 mM L-Arg, but not D-Arg, to the perfusing solution significantly increased NO2- and NO3- in the hippocampus and NO2- alone in the striatum. These increases were abolished by 1 mM N(omega)-nitro-L-arginine, an NOS inhibitor. L-Arg at 1mM was able to significantly increase NO2-, but not NO3-, in the hippocampus to a level comparable with that at 10 mM L-Arg, while it had no effect in the striatum. L-Arg (500 mg/kg, i.p.) induced a significant increase in NO2- and NO3- in the hippocampus, but not in the striatum. These results suggest that the striatum may have a lower ability to enhance NO production by utilising exogenous L-Arg than the hippocampus, despite higher basal NO production.

摘要

我们先前表明,全身给予一氧化氮(NO)前体L-精氨酸(L-Arg)未能逆转一氧化氮合酶(NOS)抑制剂对大鼠化学诱导的颤抖行为的抑制作用,从而提出了外源性L-Arg可能无法均匀供应至对NOS抑制剂敏感的脑区这一假说。因此,在本研究中,我们通过体内脑微透析,检测了外源性L-Arg对清醒大鼠海马体和纹状体这两个不同脑区中氧化型一氧化氮(NO)产物亚硝酸盐(NO2-)和硝酸盐(NO3-)细胞外水平的影响。两个脑区的基础NO2-水平相当,而海马体中的NO3-水平显著低于纹状体。向灌注液中添加10 mM L-Arg而非D-Arg,可显著增加海马体中的NO2-和NO3-,以及纹状体中单独的NO2-。这些增加被1 mM N(ω)-硝基-L-精氨酸(一种NOS抑制剂)消除。1 mM的L-Arg能够显著增加海马体中的NO2-,但不能增加NO3-,使其达到与10 mM L-Arg相当的水平,而对纹状体则无影响。腹腔注射L-Arg(500 mg/kg)可使海马体中的NO2-和NO3-显著增加,但对纹状体则无此作用。这些结果表明,尽管纹状体的基础NO生成量较高,但其利用外源性L-Arg增强NO生成的能力可能低于海马体。

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