Ackley D C, Yokel R A
College of Pharmacy, University of Kentucky Medical Center, Lexington 40536-0082, USA.
Toxicology. 1998 May 15;127(1-3):59-67. doi: 10.1016/s0300-483x(98)00037-7.
Blood brain barrier transport of aluminum citrate was assessed in rats by microdialysis of the jugular vein as well as the right and left frontal cortices. Previous studies (Allen et al., 1995. Evidence for energy-dependent transport of aluminum out of brain extracellular fluid. Toxicology 92, 193-202; Ackley and Yokel, 1997. Aluminum citrate is transported from brain into blood via the monocarboxylic acid transporter located at the blood-brain barrier. Toxicology 120, 89-97), and the current study, demonstrated that the steady-state brain-to-blood ratio of the unbound extracellular aluminum immediately surrounding the microdialysis probe is less than 1, suggesting the presence of a process other than diffusion across the blood brain barrier. It was speculated that a monocarboxylate transporter at the blood brain barrier was maintaining this ratio at less than 1 (Ackley and Yokel, 1997). Monocarboxylate transporters are proton co-transporters. Decreasing extracellular pH (increasing proton availability) increases monocarboxylate transport. After alkalinizing the dialysate perfusing a brain microdialysis probe (to pH = 10.2), the steady-state aluminum brain-to-blood ratio increased from 0.35 to 0.80. The addition of the proton ionophore, p-(trifluoromethoxy)phenylhydrazone (FCCP) (1 mM), to brain dialysate increased this ratio from 0.21 to 0.61. These increased ratios suggest that a proton-dependent process is removing Al from brain extracellular fluid. The monocarboxylate transporter is the only known proton-dependent transporter at the blood-brain barrier. There are two known isoforms of this transporter in the rodent, MCT1 and MCT2. Organomercurial thiol reagents, such as mersalyl acid, inhibit MCT1 but not MCT2. Mersalyl acid (50 mM) addition to brain dialysate increased the steady-state aluminum brain-to-blood ratio from 0.19 to 0.87, suggesting that MCT1 is at least partially mediating the efflux of aluminum from brain extracellular fluid.
通过对大鼠颈静脉以及左右额叶皮质进行微透析，评估柠檬酸铝的血脑屏障转运情况。先前的研究（Allen等人，1995年。铝从脑细胞外液中能量依赖性转运的证据。毒理学92，193 - 202；Ackley和Yokel，1997年。柠檬酸铝通过位于血脑屏障的单羧酸转运体从脑转运到血液中。毒理学120，89 - 97）以及当前的研究表明，微透析探针周围未结合的细胞外铝的稳态脑血比小于1，这表明存在除了通过血脑屏障扩散之外的其他过程。据推测，血脑屏障处的单羧酸转运体将该比例维持在小于1（Ackley和Yokel，1997年）。单羧酸转运体是质子共转运体。降低细胞外pH值（增加质子可用性）会增加单羧酸转运。在用碱化的透析液灌注脑微透析探针（至pH = 10.2）后，稳态铝脑血比从0.35增加到0.80。向脑透析液中添加质子离子载体p -（三氟甲氧基）苯腙（FCCP）（1 mM）使该比例从0.21增加到0.61。这些增加的比例表明质子依赖性过程正在从脑细胞外液中去除铝。单羧酸转运体是血脑屏障处唯一已知的质子依赖性转运体。在啮齿动物中有两种已知的该转运体同工型，MCT1和MCT2。有机汞硫醇试剂，如汞撒利酸，抑制MCT1但不抑制MCT2。向脑透析液中添加汞撒利酸（50 mM）使稳态铝脑血比从0.19增加到0.87，这表明MCT1至少部分介导了铝从脑细胞外液的流出。
