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

The Journal of Pharmacology and Experimental Therapeutics
Ken-ichi HosoyaMasanori Tachikawa

Abstract

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. Immunohistochemical 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 [(3)H]p-aminohippuric acid ([(3)H]PAH), [(3)H]benzylpenicillin ([(3)H]PCG), and [(14)C]6-mercaptopurine ([(14)C]6-MP), substrates of rOat3, from the vitreous humor/retina to the circulating blood across the inner BRB was evaluated using the microdialysis method. [(3)H]PAH, [(3)H]PCG, [(14)C]6-MP, and [(14)C] or [(3)H]d-mannitol, a bulk flow marker, were biexponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [(3)H]PAH, [(3)H]PCG, and [(14)C]6-MP during the...Continue Reading

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Citations

Nov 21, 2009·The Journal of Pharmacology and Experimental Therapeutics·Rajendra S Kadam, Uday B Kompella
Jan 28, 2010·Pharmacological Reviews·Curtis D Klaassen, Lauren M Aleksunes
Jul 2, 2009·Pharmaceutical Research·Ken-ichi Hosoya, Masanori Tachikawa
May 5, 2010·Expert Opinion on Drug Metabolism & Toxicology·Masatoshi Tomi, Ken-ichi Hosoya
Apr 27, 2012·Journal of Pharmaceutical Sciences·Yoshiyuki KuboKen-Ichi Hosoya
Feb 13, 2016·Frontiers in Cellular Neuroscience·Andrea TrostHerbert A Reitsamer
Sep 17, 2013·Translational Research : the Journal of Laboratory and Clinical Medicine·Azza A K El-SheikhFrans G M Russel
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Mar 24, 2010·Experimental Eye Research·Emiliano BuitragoGuillermo F Bramuglia
Jan 16, 2010·Experimental Eye Research·Daisuke YoneyamaKen-Ichi Hosoya
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May 3, 2018·Expert Opinion on Drug Metabolism & Toxicology·Yoshiyuki KuboKen-Ichi Hosoya
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Jul 11, 2018·Pharmaceutical Research·Shirley A AguirreWenhu Huang
Mar 14, 2018·Pharmaceutical Research·Yoshiyuki KuboKen-Ichi Hosoya

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