title: The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain.
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 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.
authors.affiliation: Department of Moleular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba Aramaki, Sendai, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Ohtsuki
authors.forename: Masanori
authors.initials: M
authors.lastname: Tachikawa
authors.forename: Hitomi
authors.initials: H
authors.lastname: Takanaga
authors.forename: Hidemi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hosoya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Terasaki
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D001692:Biological Transport / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000502:physiology; D003401:Creatine / Q000097:blood / Q000378:metabolism*; D005260:Female; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011817:Rabbits; D012964:Sodium / Q000502:physiology; D014018:Tissue Distribution
chemical_list: D002712:Chlorides; D026901:Membrane Transport Proteins; C080679:creatine transporter; D012964:Sodium; D003401:Creatine