Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium.
OBJECTIVE
The organic anion transporting protein (Oatp)-2 has been cloned from brain and retina. It mediates transport of many endogenous and exogenous amphiphilic compounds across the plasma membrane in a sodium-independent manner. In the brain it resides at the luminal and abluminal membrane of the capillary endothelium and at the basolateral membrane of the choroid plexus epithelium. In the liver, it is expressed at the basolateral membrane of hepatocytes. Its exact localization and function in the retina are unknown. Therefore, the purposes of the present study were to determine the cellular and subcellular localization and the potential functional aspects of Oatp2 in the retina.


METHODS
Oatp2 was detected in rat retinal tissue by immunofluorescence confocal microscopy and by Western blot analysis, with a specific antibody. A Xenopus laevis oocyte expression system was used for functional transport studies.


RESULTS
Oatp2 immunoreactivity was abundantly present at the apical microvilli of the rat retinal pigment epithelium and to a lesser degree in small retinal vessels. In the oocyte expression system, N-retinyl-N-retinylidene ethanolamine (A2E), an unusual cationic, amphiphilic retinoid, exhibited competitive Cis inhibition of Oatp2-mediated digoxin transport with an estimated K(i) of approximately 37 microM.


CONCLUSIONS
In rat retina, Oatp2 is localized at the interface between the pigment epithelium and the photoreceptor outer segments. A2E is a competitive inhibitor of Oatp2-mediated substrate transport, suggesting that A2E or A2E-like compounds and some retinoids may be substrates for Oatp2 transport.
Gao
Bo
B
Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, Zürich, Switzerland.
Wenzel
Andreas
A
Grimm
Christian
C
Vavricka
Stephan R
SR
Benke
Dietmar
D
Meier
Peter J
PJ
Remè
Charlotte E
CE
D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D015153:Blotting, Western; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D027381:Liver-Specific Organic Anion Transporter 1 / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008871:Microvilli / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000378:metabolism; D014982:Xenopus laevis
C112040:A2-E (N-retinylidene-N-retinylethanolamine); D027381:Liver-Specific Organic Anion Transporter 1; D012176:Retinoids