Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine

Ken Ichi Hosoya, Akihide Makihara, Yuki Tsujikawa, Daisuke Yoneyama, Shinobu Mori, Tetsuya Terasaki, Shin Ichi Akanuma, Masatoshi Tomi, Masanori Tachikawa

研究成果: Article査読

52 被引用数 (Scopus)

抄録

The purpose of the present study was to characterize rat organic anion transporter (Oat) 3 (Oat3, Slc22a8) in the efflux transport at the inner blood-retinal barrier (BRB). Reverse transcription-polymerase chain reaction analysis showed that rat (r) Oat3 mRNA is expressed in retinal vascular endothelial cells (RVECs), but not rOat1 and rOat2 mRNA. The expression of Oat3 in the retina and human cultured retinal endothelial cells was further confirmed by Western blot analysis. Immunohisto-chemical staining in RVECs showed that rOat3 is colocalized with glucose transporter 1, but not P-glycoprotein, suggesting that rOat3 is possibly located at the abluminal membrane of the RVEC. The contribution of rOat3 to the efflux of [3H]p-aminohippuric acid ([3H]PAH), [3H]benzylpenicillin ([3H]PCG), and [14C]6-mercaptopurine ([14C]6-MP), substrates of rOat3, from the vitreous humor/retina to the circulating blood across the inner BRB was evaluated using the microdialysis method. [3H]PAH, [ 3H]PCG, [14C]6-MP, and [14C] or [ 3H]D-mannitol, a bulk flow marker, were biexponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [3H]PAH, [3H]PCG, and [14C]6-MP during the terminal phase was approximately 2-fold greater than that of D-mannitol. This efflux transport was reduced in the retinal presence of probenecid, PAH, and PCG, whereas it was not inhibited by digoxin. In conclusion, rOat3 is expressed at the inner BRB and involved in the vitreous humor/retina-to-blood transport of PAH, PCG, and 6-MP. This transport system is one mechanism to limit the retinal distribution of PAH, PCG, and 6-MP.

本文言語English
ページ(範囲)87-93
ページ数7
ジャーナルJournal of Pharmacology and Experimental Therapeutics
329
1
DOI
出版ステータスPublished - 2009 4 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

フィンガープリント 「Roles of inner blood-retinal barrier organic anion transporter 3 in the vitreous/retina-to-blood efflux transport of p-aminohippuric acid, benzylpenicillin, and 6-mercaptopurine」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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