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

Research output: Contribution to journalArticle

35 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Cerebrospinal fluid
Convulsants
Cerebrospinal Fluid
Brain
Blood
Choroid Plexus
Proteins
Creatine
Epithelial Cells
creatine transporter
glycocyamine
Mannitol
Brushes
Microvilli
Rats
Seizures
Membranes
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

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

In: Journal of Neurochemistry, Vol. 107, No. 3, 11.2008, p. 768-778.

Research output: Contribution to journalArticle

Tachikawa, M, Fujinawa, J, Takahashi, M, Kasai, Y, Fukaya, M, Sakai, K, Yamazaki, M, Tomi, M, Watanabe, M, Sakimura, K, Terasaki, T & Hosoya, KI 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, vol. 107, no. 3, pp. 768-778. https://doi.org/10.1111/j.1471-4159.2008.05652.x
Tachikawa, Masanori ; Fujinawa, Jun ; Takahashi, Masato ; Kasai, Yasuyuki ; Fukaya, Masahiro ; Sakai, Kazuhisa ; Yamazaki, Maya ; Tomi, Masatoshi ; Watanabe, Masahiko ; Sakimura, Kenji ; Terasaki, Tetsuya ; Hosoya, Ken Ichi. / 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. In: Journal of Neurochemistry. 2008 ; Vol. 107, No. 3. pp. 768-778.
@article{99f689e85b104f0385ea368ff5c3b319,
title = "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",
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.",
keywords = "Blood-cerebrospinal fluid barrier, Choroid plexus, Convulsion, Creatine transporter, Expression, Guanidinoacetate",
author = "Masanori Tachikawa and Jun Fujinawa and Masato Takahashi and Yasuyuki Kasai and Masahiro Fukaya and Kazuhisa Sakai and Maya Yamazaki and Masatoshi Tomi and Masahiko Watanabe and Kenji Sakimura and Tetsuya Terasaki and Hosoya, {Ken Ichi}",
year = "2008",
month = "11",
doi = "10.1111/j.1471-4159.2008.05652.x",
language = "English",
volume = "107",
pages = "768--778",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - 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

AU - Tachikawa, Masanori

AU - Fujinawa, Jun

AU - Takahashi, Masato

AU - Kasai, Yasuyuki

AU - Fukaya, Masahiro

AU - Sakai, Kazuhisa

AU - Yamazaki, Maya

AU - Tomi, Masatoshi

AU - Watanabe, Masahiko

AU - Sakimura, Kenji

AU - Terasaki, Tetsuya

AU - Hosoya, Ken Ichi

PY - 2008/11

Y1 - 2008/11

N2 - 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.

AB - 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.

KW - Blood-cerebrospinal fluid barrier

KW - Choroid plexus

KW - Convulsion

KW - Creatine transporter

KW - Expression

KW - Guanidinoacetate

UR - http://www.scopus.com/inward/record.url?scp=53149101457&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53149101457&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2008.05652.x

DO - 10.1111/j.1471-4159.2008.05652.x

M3 - Article

VL - 107

SP - 768

EP - 778

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -