PT  - JOURNAL ARTICLE
AU  - Masanori Tachikawa
AU  - Kazuhiro Tsuji
AU  - Reiji Yokoyama
AU  - Takanori Higuchi
AU  - Go Ozeki
AU  - Ayane Yashiki
AU  - Shin-ichi Akanuma
AU  - Kazuyuki Hayashi
AU  - Akio Nishiura
AU  - Ken-ichi Hosoya
TI  - A Clearance System for Prostaglandin D<sub>2</sub>, a Sleep-Promoting Factor, in Cerebrospinal Fluid: Role of the Blood-Cerebrospinal Barrier Transporters
AID  - 10.1124/jpet.112.197012
DP  - 2012 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 608--616
VI  - 343
IP  - 3
4099  - http://jpet.aspetjournals.org/content/343/3/608.short
4100  - http://jpet.aspetjournals.org/content/343/3/608.full
SO  - J Pharmacol Exp Ther2012 Dec 01; 343
AB  - 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.