The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain

Sumio Ohtsuki, Masanori Tachikawa, Hitomi Takanaga, Hidemi Shimizu, Masahiko Watanabe, Ken ichi Hosoya, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

147 Citations (Scopus)


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 β-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.

Original languageEnglish
Pages (from-to)1327-1335
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number11
Publication statusPublished - 2002 Nov 1
Externally publishedYes


  • Blood-brain barrier
  • Brain capillary endothelial cell
  • Carrier-mediated transport
  • Creatine
  • Creatine transporter
  • Phosphate-bound energy sources

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine


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