Cationic amino acid transporter 1-mediated l-arginine transport at the inner blood–retinal barrier |
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Authors: | Masatoshi Tomi Naohisa Kitade Shirou Hirose Noriko Yokota Shin-ichi Akanuma Masanori Tachikawa Ken-ichi Hosoya |
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Institution: | Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan |
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Abstract: | The purpose of this study was to identify the transporter mediating l -arginine transport at the inner blood–retinal barrier (BRB). The apparent uptake clearance of 3H] l -arginine into the rat retina was found to be 118 μL/(min·g retina), supporting a carrier-mediated influx transport of l -arginine at the BRB. 3H] l -Arginine uptake by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), used as an in vitro model of the inner BRB, was primarily an Na+-independent and saturable process with Michaelis-Menten constants of 11.2 μM and 530 μM. This process was inhibited by rat cationic amino acid transporter (CAT) 1-specific small interfering RNA as well as substrates of CATs, l -arginine, l -lysine, and l -ornithine. The expression of cationic amino acid transporter (CAT) 1 mRNA was 25.9- and 796-fold greater than that of CAT3 in TR-iBRB2 and magnetically isolated rat retinal vascular endothelial cells, respectively. The expression of CAT1 protein was detected in TR-iBRB2 cells and immunostaining of CAT1 was observed along the rat retinal capillaries. In conclusion, CAT1 is localized in retinal capillary endothelial cells and at least in part mediates l -arginine transport at the inner BRB. This process seems to be closely involved in visual functions by supplying precursors of biologically important molecules like nitric oxide in the neural retina. |
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Keywords: | arginine capillary endothelial cells cationic amino acid transporter inner blood–retinal barrier retina transport |
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