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牛磺酸的脑-血外排转运以及肿瘤坏死因子-α对血脑屏障转运系统的影响。

The brain-to-blood efflux transport of taurine and changes in the blood-brain barrier transport system by tumor necrosis factor-alpha.

作者信息

Lee Na-Young, Kang Young-Sook

机构信息

College of Pharmacy, Sookmyung Women's University, 53-12, Chungpa-Dong 2 Ka, Yongsan-Gu, Seoul 140-742, Korea.

出版信息

Brain Res. 2004 Oct 8;1023(1):141-7. doi: 10.1016/j.brainres.2004.07.033.

Abstract

The purpose of this study was to examine whether the efflux transport system for taurine from brain to blood is present at the blood-brain barrier (BBB) by using the brain efflux index (BEI) method and to determine whether the taurine transport system is regulated after central nervous system cell damage by tumor necrosis factor-alpha (TNF-alpha) in vivo. [(3)H]Taurine was microinjected into the parietal cortex area 2 of the rat brain, and was eliminated from the brain with an efflux transport rate of 1.22 x 10(-2) min(-1), and the process is saturable with a K(m) of 39.1 microM. This process was significantly inhibited by taurine transporter (TAUT) inhibitors, such as unlabeled taurine, beta-alanine, betaine, nipecotic acid and gamma-aminobutyric acid (GABA). In addition, the effect of tumor necrosis factor-alpha on [(3)H]taurine transport was investigated. [(3)H]Taurine uptake was increased and its efflux was reduced by pretreatment with tumor necrosis factor-alpha. Also, [(3)H]taurine efflux was reduced by tumor necrosis factor-alpha in a time- and dose-dependent manner. In conclusion, there is the efflux pump for taurine at the blood-brain barrier to reduce taurine concentration in the brain interstitial fluid, and this process was carrier mediated. In addition, the transport system for taurine through the blood-brain barrier was found to be regulated by tumor necrosis factor-alpha in vivo.

摘要

本研究的目的是通过使用脑外排指数(BEI)方法来检测血脑屏障(BBB)处是否存在从脑到血液的牛磺酸外排转运系统,并确定在体内中枢神经系统细胞受到肿瘤坏死因子-α(TNF-α)损伤后牛磺酸转运系统是否受到调节。将[³H]牛磺酸微量注射到大鼠脑顶叶皮质2区,其以1.22×10⁻² min⁻¹的外排转运速率从脑中消除,且该过程具有饱和性,米氏常数(Kₘ)为39.1 μM。该过程受到牛磺酸转运体(TAUT)抑制剂的显著抑制,如未标记的牛磺酸、β-丙氨酸、甜菜碱、哌啶酸和γ-氨基丁酸(GABA)。此外,研究了肿瘤坏死因子-α对[³H]牛磺酸转运的影响。用肿瘤坏死因子-α预处理可增加[³H]牛磺酸的摄取并降低其外排。而且,肿瘤坏死因子-α以时间和剂量依赖性方式降低[³H]牛磺酸的外排。总之,血脑屏障处存在牛磺酸外排泵以降低脑间质液中牛磺酸的浓度,且该过程由载体介导。此外,发现牛磺酸通过血脑屏障的转运系统在体内受到肿瘤坏死因子-α的调节。

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