Expression and possible role of creatine transporter in the brain and at the blood-cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant

Masanori Tachikawa, Jun Fujinawa, Masato Takahashi, Yasuyuki Kasai, Masahiro Fukaya, Kazuhisa Sakai, Maya Yamazaki, Masatoshi Tomi, Masahiko Watanabe, Kenji Sakimura, Tetsuya Terasaki, Ken Ichi Hosoya

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Abstract

Little is known about the cerebral distribution and clearance of guanidinoacetate (GAA), the accumulation of which induces convulsions. The purpose of the present study was to identify creatine transporter (CRT)-mediated GAA transport and to clarify its cerebral expression and role in GAA efflux transport at the blood-cerebrospinal fluid barrier (BCSFB). CRT mediated GAA transport with a Km value of 269 μM/412 μM which was approximately 10-fold greater than that of CRT for creatine. There was wide and distinct cerebral expression of CRT and localization of CRT on the brush-border membrane of choroid plexus epithelial cells. The in vivo elimination clearance of GAA from the CSF was 13-fold greater than that of d-mannitol reflecting bulk flow of the CSF. This process was partially inhibited by creatine. The characteristics of GAA uptake by isolated choroid plexus and an immortalized rat choroid plexus epithelial cell line (TR-CSFB cells) used as an in vitro model of BCSFB are partially consistent with those of CRT. These results suggest that CRT plays a role in the cerebral distribution of GAA and GAA uptake by the choroid plexus. However, in the presence of endogenous creatine in the CSF, CRT may make only a limited contribution to the GAA efflux transport at the BCSFB.

Original languageEnglish
Pages (from-to)768-778
Number of pages11
JournalJournal of Neurochemistry
Volume107
Issue number3
DOIs
Publication statusPublished - 2008 Nov 1
Externally publishedYes

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Keywords

  • Blood-cerebrospinal fluid barrier
  • Choroid plexus
  • Convulsion
  • Creatine transporter
  • Expression
  • Guanidinoacetate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Tachikawa, M., Fujinawa, J., Takahashi, M., Kasai, Y., Fukaya, M., Sakai, K., Yamazaki, M., Tomi, M., Watanabe, M., Sakimura, K., Terasaki, T., & Hosoya, K. I. (2008). Expression and possible role of creatine transporter in the brain and at the blood-cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant. Journal of Neurochemistry, 107(3), 768-778. https://doi.org/10.1111/j.1471-4159.2008.05652.x