Involvement of the carrier-mediated process in the retina-to-blood transport of spermine at the inner blood-retinal barrier.
The elimination of spermine, the end product of cellular polyamine, from the retina to the blood across the blood-retinal barrier (BRB) was investigated. The in vivo microdialysis study revealed that the elimination of [(3)H]spermine from vitreous humor after vitreous bolus injection was in a biexponential manner. The rate constant for the elimination of [(3)H]spermine during the terminal phase was estimated to be 1.67-fold greater than that of [(14)C]d-mannitol, a bulk flow marker, and the difference in the terminal elimination rate constant between [(3)H]spermine and [(14)C]d-mannitol was reduced in the presence of 50 mM spermine, suggesting a retina-to-blood transport system for [(3)H]spermine across the BRB. The retina-to-blood transport of [(3)H]spermine was also supported by a study of the retinal uptake index (RUI). The in vitro transport study with TR-iBRB2 cells, a model cell line of the inner BRB, revealed time-, concentration- and temperature-dependent transport of [(3)H]spermine, suggesting the involvement of carrier-mediated processes in spermine transport across the inner BRB. The in vitro study also suggested that the transport of spermine at the inner BRB is pH-, membrane potential- and Cl(-)-sensitive and Na(+)-insensitive, and these functional properties of spermine transport suggest only a minor contribution of spermine transporters, such as CCC9 (SLC12A8), the expression of which was suggested at the inner BRB. In the inhibition study, [(3)H]spermine transport was markedly inhibited by putrescine, spermidine, spermine and agmatine while substrates of a well-characterized organic cation transporter (OCTs/SLC22A) and a cationic amino acid transporter (CATs/SLC7A) had no effect, suggesting the involvement of unknown transporters in spermine elimination from the retina.
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
Yoshiyuki
Y
Kubo
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
Ayaka
A
Tomise
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
Ai
A
Tsuchiyama
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan.
Shin-Ichi
S
Akanuma
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630, Sugitani, Toyama 930-0194, Japan. Electronic address: hosoyak@pha.u-toyama.ac.jp.
Ken-Ichi
K
Hosoya
D000818:Animals; D001692:Biological Transport; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002460:Cell Line; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism*
D026901:Membrane Transport Proteins; D013096:Spermine
blood-retinal barrier; polyamine; polyamine transporter; spermine; transport