TY - JOUR
T1 - Application of microdialysis to evaluate the efflux transport of estradiol 17-β glucuronide across the rat blood-retinal barrier
AU - Katayama, Kazunori
AU - Ohshima, Yuki
AU - Tomi, Masatoshi
AU - Hosoya, Ken ichi
N1 - Funding Information:
The authors would like to thank Dr. Junichi Kawakami for valuable discussions. This study was supported, in part, by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and a grant for Research on Sensory and Communicative Disorders by the Ministry of Health, Labor, and Welfare, Japan.
PY - 2006/9/30
Y1 - 2006/9/30
N2 - 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-β glucuronide (E17βG) across the blood-retinal barrier (BRB) by the use of microdialysis. [3H]E17βG and [14C]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. [3H]E17βG and [14C]d-mannitol were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [3H]E17βG during the terminal phase was 1.9-fold greater than that of [14C]d-mannitol and reduced the level of [14C]d-mannitol in the retinal presence of 0.3 mM E17βG, suggesting that [3H]E17βG is transported via a carrier-mediated efflux transport process across the BRB. The efflux transport of [3H]E17βG 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 [3H]E17βG across the rat BRB was evaluated by microdialysis and its inhibition by organic anions suggests organic anion transporting polypeptide 1a4-mediated E17βG efflux transport at the BRB.
AB - 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-β glucuronide (E17βG) across the blood-retinal barrier (BRB) by the use of microdialysis. [3H]E17βG and [14C]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. [3H]E17βG and [14C]d-mannitol were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [3H]E17βG during the terminal phase was 1.9-fold greater than that of [14C]d-mannitol and reduced the level of [14C]d-mannitol in the retinal presence of 0.3 mM E17βG, suggesting that [3H]E17βG is transported via a carrier-mediated efflux transport process across the BRB. The efflux transport of [3H]E17βG 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 [3H]E17βG across the rat BRB was evaluated by microdialysis and its inhibition by organic anions suggests organic anion transporting polypeptide 1a4-mediated E17βG efflux transport at the BRB.
KW - Blood-retinal barrier
KW - Efflux transport
KW - Microdialysis
KW - Organic anion
KW - Organic anion transporting polypeptide (Oatp)1a4
UR - http://www.scopus.com/inward/record.url?scp=33747198077&partnerID=8YFLogxK
U2 - 10.1016/j.jneumeth.2006.03.012
DO - 10.1016/j.jneumeth.2006.03.012
M3 - 学術論文
C2 - 16621011
AN - SCOPUS:33747198077
SN - 0165-0270
VL - 156
SP - 249
EP - 256
JO - Journal of Neuroscience Methods
JF - Journal of Neuroscience Methods
IS - 1-2
ER -