谷胱甘肽在大鼠血脑屏障中的运输：谷胱甘肽类似物的抑制和年龄依赖性。,Journal of Pharmacology and Experimental Therapeutics

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谷胱甘肽在大鼠血脑屏障中的运输：谷胱甘肽类似物的抑制和年龄依赖性。
Journal of Pharmacology and Experimental Therapeutics ( IF 3.1 ) Pub Date : 1992-12-01
R Kannan ₁ , J F Kuhlenkamp , M Ookhtens , N Kaplowitz

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先前我们已经表明，谷胱甘肽（GSH）可以通过可饱和的低亲和力转运过程（Km约为6 mM）完整地穿过血脑屏障（Kannan等，J。Clin。Invest。85：2009-2013，1990）。在本报告中，进一步排除了GSH的分解和再合成作为表观GSH摄取的机制，因为在血脑屏障处摄取的注射的35S-半胱氨酸中> 87％保持不变，而掺入GSH的程度可忽略不计。为了进一步表征该GSH转运系统，我们研究了多种潜在抑制剂对用γ-谷氨酰转肽酶抑制剂阿西维林预处理的大鼠中GSH的脑摄取指数（BUI）的影响。在存在或不存在1至20 mM半胱氨酸，谷胱甘肽二硫化物，γ-谷氨酰胺基谷氨酸盐的情况下，示踪剂35S-GSH的BUI摄取 γ-谷氨酰基-对硝基苯胺和2-氨基双环（2,2,1）庚烷-2-羧酸之间没有显着差异。但是，S-烷基谷胱甘肽（己基和辛基），磺基溴酞-谷胱甘肽，谷胱甘肽单乙酯，丙磺舒（5 mM）和邻苯二甲酸（10 mM）显着抑制了GSH的吸收。磺基溴酞-谷胱甘肽和GSH-单乙酯对GSH吸收的抑制是浓度依赖性的，表观Ki分别约为0.016和0.083 mM。在25至135日龄（100-500 g b.wt.）的生长和发育期间，用阿西维林和非阿西维辛预处理的大鼠的GSH-BUI均随着年龄的增长而下降。BUI随年龄的下降是GSH特有的；

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Transport of glutathione at blood-brain barrier of the rat: inhibition by glutathione analogs and age-dependence.

We showed previously that glutathione (GSH) may cross the blood-brain barrier intact by a saturable low affinity transport process (Km approximately 6 mM) (Kannan et al., J. Clin. Invest. 85: 2009-2013, 1990). In the present report, breakdown and resynthesis of GSH as the mechanism of apparent GSH uptake were excluded further because > 87% of injected 35S-cysteine taken up at the blood-brain barrier remained unchanged with negligible incorporation into GSH. In an effort to characterize further this GSH transport system, we have studied the influence of a number of potential inhibitors on brain uptake index (BUI) of GSH in rats pretreated with a gamma-glutamyl transpeptidase inhibitor, acivicin. The BUIs of tracer 35S-GSH uptake in the presence or absence of 1 to 20 mM cysteine, glutathione disulfide, gamma-glutamylglutamate, gamma-glutamyl-p-nitroanilide and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid did not differ significantly from each other. However, S-alkyl glutathiones (hexyl and octyl), sulfobromophthalein-glutathione, glutathione monoethyl ester, probenecid (5 mM) and ophthalmic acid (10 mM) inhibited GSH uptake significantly. Inhibition of GSH uptake by sulfobromophthalein-glutathione and GSH-monoethyl ester was concentration-dependent with apparent Ki approximately 0.016 and 0.083 mM, respectively. There was a decline in GSH-BUI as a function of age in both acivicin and nonacivicin-pretreated rats during the growth and developmental period from 25 to 135 days of age (100-500 g b.wt.). The decrease in BUI with age was specific for GSH; cysteine uptake did not change and no difference in diffusible (H2O) and nondiffusible (sucrose) components was found in this age range.(ABSTRACT TRUNCATED AT 250 WORDS)

更新日期：2019-11-01

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