1. ^*Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan
2. ^†New Industry Creation Hatchery Center, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan
3. ^‡CREST of Japan Science and Technology Corporation, Sapporo, Japan
4. ^§Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan
5. Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan

Correspondence: Tetsuya Terasaki, Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan; e-mail: terasaki@mail.pharm.tohoku.ac.jp

Received 19 April 2002; Revised 26 July 2002; Accepted 30 July 2002.

Abstract

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 in vivo 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 -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.