A clearance system for prostaglandin D2, a sleep-promoting factor, in cerebrospinal fluid: Role of the blood-cerebrospinal barrier transporters

Masanori Tachikawa, Kazuhiro Tsuji, Reiji Yokoyama, Takanori Higuchi, Go Ozeki, Ayane Yashiki, Shin Ichi Akanuma, Kazuyuki Hayashi, Akio Nishiura, Ken Ichi Hosoya

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Although the level of prostaglandin (PG) D2 in cerebrospinal fluid (CSF) affects the action of D-type prostanoid receptors that promote physiological sleep, the regulatory system of PGD2 clearance from the CSF is not fully understood. The purpose of this study was to investigate PGD2 elimination from the CSF via the blood-CSF barrier (BCSFB). The in vivo PGD2 elimination clearance from the CSF was 16-fold greater than that of inulin, which is considered to reflect CSF bulk flow. This process was inhibited by the simultaneous injection of unlabeled PGD2. The characteristics of PGD2 uptake by isolated choroid plexus were, at least partially, consistent with those of PG transporter (PGT) and organic anion transporter 3 (OAT3). Studies using an oocyte expression system showed that PGT and OAT3 were able to mediate PGD2 transport with a Michaelis-Menten constant of 1.07 and 7.32 μM, respectively. Reverse transcription-polymerase chain reaction and immunohistochemical analyses revealed that PGT was localized on the brush-border membrane of the choroid plexus epithelial cells. These findings indicate that the system regulating the PGD2 level in the CSF involves PGT- and OAT3-mediated PGD2 uptake by the choroid plexus epithelial cells, acting as a pathway for PGD2 clearance from the CSF via the BCSFB.

Original languageEnglish
Pages (from-to)608-616
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume343
Issue number3
DOIs
Publication statusPublished - 2012 Dec

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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