Localization of organic anion transporting polypeptides in the rat and human ciliary body epithelium.
OBJECTIVE
To identify and localize the expression of multispecific organic anion transporting polypeptides (Oatps/OATPs) in the ciliary body epithelium and to investigate their possible involvement in the transport of the antiglaucoma agent unoprostone.


METHODS
Oatps/OATPs were detected by immunoblot analysis and by immunofluorescence microscopy in homogenized and fixed rat and human ciliary body samples using specific polyclonal antibodies. Transport of 3H-labelled unoprostone was measured in Oatp/OATP expressing Xenopus laevis oocytes.


RESULTS
Immunoblots of ciliary body extracts were positive for rat Oatp1a4, Oatp1a5 and Oatp1b2 and for human OATP1A2, OATP1C1, OATP2B1, OATP3A1 and OATP4A1. Confocal immunofluorescence microscopy localized Oatp1a4 and Oatp1b2 as well as all immunoblot positive human OATPs at the basolateral plasma membrane of the non-pigmented rat and human ciliary body epithelium, respectively. However, for human OATPs additional regional differences in expression were found with OATP1A2 and OATP1C1 being expressed only in the pars plana of human ciliary body epithelium. Furthermore, OATP1C1, OATP3A1 and OATP4A1 were also expressed at the basolateral plasma membrane of the pars plana pigmented epithelium. And finally, deesterified unoprostone carboxylate was found to be transported by OATP1A2, OATP2B1 and OATP4A1 with approximate K(m)-values of 93, 91 and 132 microm, respectively.


CONCLUSIONS
Several multispecific organic anion transporting polypeptides are expressed at the basolateral plasma membrane of the non-pigmented, and to a lesser extent also of the pigmented, epithelium in rat and human ciliary body. These Oatps/OATPs can account for the previously suggested 'liver-like' transport functions of mammalian ciliary body epithelium.
Gao
Bo
B
Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital Zurich, CH-8091 Zurich, Switzerland.
Huber
Robert D
RD
Wenzel
Andreas
A
Vavricka
Stephan R
SR
Ismair
Manfred G
MG
Remé
Charlotte
C
Meier
Peter J
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D000959:Antihypertensive Agents / Q000032:analysis; D001692:Biological Transport; D002460:Cell Line; D002924:Ciliary Body / Q000276:immunology / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1 / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D027362:Organic Anion Transport Protein 1 / Q000032:analysis / Q000378:metabolism; D027361:Organic Anion Transporters / Q000032:analysis* / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN
D000959:Antihypertensive Agents; D027381:Liver-Specific Organic Anion Transporter 1; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D010455:Peptides; C479544:SLCO3A1 protein, human; C498174:SLCO4A1 protein, human; C072630:isopropyl unoprostone; D015237:Dinoprost