Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier.

Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. Research Abstract Details 

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Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. Abstract Text:

Sumio Ohtsuki,Shingo Ito,Akihiro Matsuda,Satoko Hori,Takaaki Abe,Tetsuya Terasaki,Sumio Ohtsuki,Shingo Ito,Akihiro Matsuda,Satoko Hori,Takaaki Abe,Tetsuya Terasaki,

24S-Hydroxycholesterol (24S-OH-chol), a major cerebral cholesterol metabolite, is an endogenous ligand for the liver X receptor and is a potential stimulant of cholesterol release from glial cells. The elimination mechanism of 24S-OH-chol from the brain is one of the key issues for understanding cerebral cholesterol homeostasis. The purpose of the present study was to clarify the molecular mechanism of the elimination process of 24S-OH-chol across the blood-brain barrier (BBB). After an intracerebral injection in rats, [(3)H]24S-OH-chol was eliminated from the brain and the radioactivity derived from [(3)H]24S-OH-chol was detected in the plasma, while [(3)H]cholesterol was not significantly eliminated from the brain. Co-administration of unlabeled 24S-OH-chol significantly inhibited the [(3)H]24S-OH-chol elimination, while no inhibitory effect was seen at the same concentration of cholesterol. The [(3)H]24S-OH-chol elimination was inhibited by co-administration of probenecid, but not by benzylpenicillin. Pre-administration of digoxin completely inhibited the elimination. Xenopus laevis oocytes expressing rat oatp2 exhibited significant transport of [(3)H]24S-OH-chol, and this was inhibited by unlabeled 24S-OH-chol and digoxin, indicating that rat oatp2 transports 24S-OH-chol. These results are the first direct demonstration that 24S-OH-chol undergoes elimination from the brain to blood across the BBB via a carrier-mediated process, which involves oatp2 expressed at the BBB in rats.

Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. Publishing Authors By Initials

S Ohtsuki,S Ito,A Matsuda,S Hori,T Abe,T Terasaki,S Ohtsuki,S Ito,A Matsuda,S Hori,T Abe,T Terasaki,

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Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of neurochemistry

VOLUME: 103

Page Numbers: 1430-8

Journal Abbreviation: J. Neurochem.

ISSN: 1471-4159

DAY: 14

MONTH: 09

YEAR: 2007

Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. Information

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LANGUAGE: eng

NlmUniqueID: 2985190

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AFFILIATION: Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan.

Country: England

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MEDLINETA: J Neurochem

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