Application of microdialysis to evaluate the efflux transport of estradiol 17-beta glucuronide across the rat blood-retinal barrier.
The purpose of the present study was to evaluate vitreous humor/retina-to-blood efflux transport in rats and determine the efflux transport of estradiol 17-beta glucuronide (E17betaG) across the blood-retinal barrier (BRB) by the use of microdialysis. [(3)H]E17betaG and [(14)C]D-mannitol, which were used as a model compound for amphipathic organic anions and a bulk flow marker, respectively, were injected into the vitreous humor of rat eye, and a microdialysis probe was placed in the vitreous humor. [(3)H]E17betaG and [(14)C]D-mannitol were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [(3)H]E17betaG during the terminal phase was 1.9-fold greater than that of [(14)C]D-mannitol and reduced the level of [(14)C]D-mannitol in the retinal presence of 0.3 mM E17betaG, suggesting that [(3)H]E17betaG is transported via a carrier-mediated efflux transport process across the BRB. The efflux transport of [(3)H]E17betaG was significantly inhibited by organic anions, such as probenecid, sulfobromophthalein, digoxin, and dehydroepiandrosterone sulfate, whereas it was not inhibited by p-aminohippuric acid. In conclusion, the efflux transport of [(3)H]E17betaG across the rat BRB was evaluated by microdialysis and its inhibition by organic anions suggests organic anion transporting polypeptide 1a4-mediated E17betaG efflux transport at the BRB.
Katayama
Kazunori
K
Department of Pharmaceutics, Graduate School of Medical and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Ohshima
Yuki
Y
Tomi
Masatoshi
M
Hosoya
Ken-ichi
K
D000465:Algorithms; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001693:Biological Transport, Active; D001813:Blood-Retinal Barrier / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D007202:Indicators and Reagents; D008297:Male; D008353:Mannitol / Q000378:metabolism; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism
D007202:Indicators and Reagents; D008353:Mannitol; D004958:Estradiol