Inner Blood–Retinal Barrier Mediates L-Isomer-Predominant Transport of Serine

作者: Masanori Tachikawa , Masashi Okamoto , Shirou Hirose , Daisuke Yoneyama , Shin-ichi Akanuma

DOI: 10.1002/JPS.22626

关键词: BiochemistryGlutamate receptorBlood–brain barrierBlood–retinal barrierRetinaSerine racemaseEndothelial stem cellSerineMolecular biologyBiologyCell culturePharmaceutical Science

摘要: D-serine, a coagonist for N-methyl-D-aspartate-type glutamate receptors, which mediate visual signal transmission, is thought to be generated from L-serine via serine racemase in the retina. However, source of and D-serine retina are yet determined. The purpose present study was investigate characteristics blood-to-retina transport at inner blood-retinal barrier (BRB). In vivo revealed [(3) H]L-serine with an influx clearance 49.9 μL/(min·g retina), greater than that H]D-serine. This consistent L-isomer-predominant uptake by conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), vitro BRB model. H]L-Serine H]D-serine TR-iBRB2 cells took place Na(+)-dependent concentration-dependent manner Michaelis constant values 97.5 μM 9.63 mM, respectively. process significantly inhibited system ASC (alanine-serine-cysteine) substrates. Polymerase chain reaction analysis immunocytochemistry expression transporters ASCT1 ASCT2 cells. These results suggest potent pathway supplying form L-isomer circulating blood

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