Brain uptake, retention, and efflux of aluminum and manganese.
Brain uptake, retention, and efflux of aluminum and manganese.
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DOI：
10.1289/ehp.02110s5699
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发表时间：
2002-10
影响因子：
10.4
通讯作者：
Yokel RA
中科院分区：
文献类型：
--
作者：
Yokel RA
我和我的同事研究了铝（Al）和锰（Mn）通过血脑屏障（BBB）分布的部位和机制。采用微透析法对血液（血浆）和脑细胞外液（ECF）中非蛋白结合铝进行了采样。静脉注射柠檬酸铝后，脑ECF铝外观太快，归因于扩散或转铁蛋白受体介导的内吞作用，这表明另一个载体介导的过程。在恒定的血液和脑ECF Al浓度下，脑：血液ECF Al浓度比为0.15，表明载体介导的脑Al流出。药理学操作表明外排载体可能是单羧酸转运蛋白（MCT）。然而，大鼠红细胞中Al（14）C-柠檬酸盐摄取的缺乏表明其不是亚型MCT 1或带3阴离子交换剂的良好底物。小鼠脑内皮细胞对Al（14）C-柠檬酸盐的摄取似乎是载体介导的，不依赖于Na、pH和能量。摄取受到MCT和有机阴离子转运蛋白家族底物/抑制剂的抑制。大鼠静脉注射~（26）Al后不同时间脑内~（26）Al的测定表明，~（26）Al的脑半衰期延长。铝转铁蛋白和柠檬酸铝通过不同的机制穿过血脑屏障，进入脑ECF的铝大部分迅速流出，可能是柠檬酸铝，但有些铝保留了相当长的一段时间。用原位脑灌注技术测定的Mn（2+）离子和柠檬酸锰的脑内流大于扩散，表明载体介导的摄取。柠檬酸锰摄取量约为Mn（2+）离子的3倍，表明其是进入大脑的主要Mn物质。在Mn（2+）离子，Mn柠檬酸盐，或Mn转铁蛋白注射到脑中，脑Mn流出并不更快，从扩散预测。Al和Mn的BBB渗透是由载体介导的，载体可能有助于调节它们的脑浓度。
My colleagues and I investigated the sites and mechanisms of aluminum (Al) and manganese (Mn) distribution through the blood-brain barrier (BBB). Microdialysis was used to sample non-protein-bound Al in the extracellular fluid (ECF) of blood (plasma) and brain. Brain ECF Al appearance after intravenous Al citrate injection was too rapid to attribute to diffusion or to transferrin-receptor-mediated endocytosis, suggesting another carrier-mediated process. The brain:blood ECF Al concentration ratio was 0.15 at constant blood and brain ECF Al concentrations, suggesting carrier-mediated brain Al efflux. Pharmacological manipulations suggested the efflux carrier might be a monocarboxylate transporter (MCT). However, the lack of Al (14)C-citrate uptake into rat erythrocytes suggested it is not a good substrate for isoform MCT1 or for the band 3 anion exchanger. Al (14)C-citrate uptake into murine-derived brain endothelial cells appeared to be carrier mediated, Na independent, pH independent, and energy dependent. Uptake was inhibited by substrate/inhibitors of the MCT and organic anion transporter families. Determination of (26)Al in rat brain at various times after intravenous (26)Al suggested a prolonged brain (26)Al half-life. It appears that Al transferrin and Al citrate cross the BBB by different mechanisms, that much of the Al entering brain ECF is rapidly effluxed, probably as Al citrate, but that some Al is retained for quite some time. Brain influx of the Mn(2+) ion and Mn citrate, determined with the in situ brain perfusion technique, was greater than that attributable to diffusion, suggesting carrier-mediated uptake. Mn citrate uptake was approximately 3-fold greater than the Mn(2+) ion, suggesting it is a primary Mn species entering the brain. After Mn(2+) ion, Mn citrate, or Mn transferrin injection into the brain, brain Mn efflux was not more rapid than that predicted from diffusion. The BBB permeation of Al and Mn is mediated by carriers that may help regulate their brain concentrations.
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影响因子：
3.8
作者：
Brenneman, KA;Wong, BA;Dorman, DC
通讯作者：
Dorman, DC
影响因子：
4.1
作者：
Divine, KK;Lewis, JL;Bench, G
通讯作者：
Bench, G
影响因子：
3.9
作者：
HARRIS, WR;CHEN, Y
通讯作者：
CHEN, Y
DOI：
10.1111/j.1748-1716.1963.tb02652.x
发表时间：
1963-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
CRONE, C
通讯作者：
CRONE, C
影响因子：
3.8
作者：
ASCHNER, M;GANNON, M
通讯作者：
GANNON, M