Ohtsuki Sumio, Tachikawa Masanori, Takanaga Hitomi, Shimizu Hidemi, Watanabe Masahiko, Hosoya Ken-Ichi, Terasaki Tetsuya
Department of Moleular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Sendai, Japan.
J Cereb Blood Flow Metab. 2002 Nov;22(11):1327-35. doi: 10.1097/01.WCB.0000033966.83623.7D.
Although creatine plays a pivotal role in the storage of phosphate-bound energy in the brain, the source of cerebral creatine is still unclear. The authors examined the contribution made by the creatine transporter (CRT) at the blood-brain barrier in supplying creatine to the brain from blood. An intravenous administration study suggested that creatine is continuously transported from the blood to the brain against the creatine concentration gradient that exists between brain and blood. Conditionally immortalized mouse brain capillary endothelial cells (TM-BBB) exhibited creatine uptake, which is Na+ and Cl- dependent and inhibited by CRT inhibitors, such as beta-guanidinopropionate and guanidinoacetate. Northern blot and immunoblot analyses demonstrated that CRT is expressed in TM-BBB cells and isolated mouse brain microvessels. Moreover, high expression of CRT was observed in the mouse brain capillaries by confocal immunofluorescent microscopy. These results suggest that CRT plays an important role in supplying creatine to the brain via the blood-brain barrier.
尽管肌酸在大脑中磷酸结合能的储存中起着关键作用，但大脑中肌酸的来源仍不清楚。作者研究了血脑屏障处的肌酸转运体（CRT）在从血液向大脑供应肌酸方面所起的作用。一项静脉给药研究表明，肌酸能逆着大脑和血液之间存在的肌酸浓度梯度持续从血液转运至大脑。条件永生化小鼠脑微血管内皮细胞（TM-BBB）表现出肌酸摄取，这种摄取依赖于Na+和Cl-，并受到CRT抑制剂（如β-胍基丙酸和胍基乙酸）的抑制。Northern印迹和免疫印迹分析表明，CRT在TM-BBB细胞和分离的小鼠脑微血管中表达。此外，通过共聚焦免疫荧光显微镜观察到小鼠脑毛细血管中CRT的高表达。这些结果表明，CRT在通过血脑屏障向大脑供应肌酸方面起着重要作用。
