Involvement of system A in the retina-to-blood transport of l-proline across the inner blood–retinal barrier

Lipophilicity and Transporter Influence on Blood-Retinal Barrier Permeability: A Comparison with Blood-Brain Barrier Permeability

“…The present study extends this observation to include a wide variety of compounds. [ 3 H]PAH and [ 14 C]MeAIB are substrates of OAT3 and system A (ATA2/Slc38a2), respectively, which are expressed at the inner BRB and exhibit an uptake function at the abluminal (retinal) side (9,28). Thus, both compounds are most likely transported via passive diffusion in the blood-to-retina/vitreous humor direction (24,29).…”

A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma

“…Zlokovic et al46 used the brain uptake index (BUI) method and found that the BUI value of [ 14 C]MeAIB (2.71%) is close to that of [ 14 C]sucrose (2.32%). In contrast, system A, most likely ATA2, is functionally expressed on the abluminal membrane of retinal/brain capillary endothelial cells and it mediates the retina/brain‐to‐blood efflux transport of l ‐proline 24,25. Thus, l ‐serine uptake by TR‐iBRB2 cells and TR‐BBB13 cells may reflect the uptake by both the luminal and abluminal membranes of capillary endothelial cells due to a lack of polarity.…”

“…The transport of d ‐serine is mediated by system ASC,20 system B 0+ ,17 and system asc 18. Of these transport systems it has been reported that alanine–serine–cysteine transporter 1 (ASCT1/SLC1A4)21 and ASCT2/SLC1A522,23 (isoforms of system ASC), sodium‐coupled neutral amino acid transporter 2 (SNAT2/ATA2/SLC38A2)24,25 (an isoform of system A), and l ‐type amino acid transporter 1 (LAT1/SLC7A5)26,27 (an isoform of system L) are expressed at the inner BRB and/or BBB. Because reverse transcription polymerase chain reaction (RT–PCR) analyses reveal that amino acid transporter B 0+ (ATB 0+ ) (an isoform of system B 0+ ) mRNA is not expressed in isolated brain capillaries and conditionally immortalized rat retinal/brain capillary endothelial cell lines (TR‐iBRB2 and TR‐BBB13 cells), an in vitro model of the inner BRB/BBB,23,28 the contribution of ATB 0+ to l ‐serine and d ‐serine uptakes can be negligible at the inner BRB and BBB.…”

Carrier-Mediated Transport of Nicotine Across the Inner Blood–Retinal Barrier: Involvement of a Novel Organic Cation Transporter Driven by an Outward H+ Gradient

“…As described previously, TR‐iBRB2 cells, a conditionally immortalized rat retinal capillary endothelial cell line, was cultured at 33°C to allow temperature‐sensitive large T‐antigen expression. Cells were washed three times with extracellular fluid (ECF) buffer [122 mM NaCl, 25 mM NaHCO 3 , 3 mM KCl, 0.4 mM K 2 HPO 4 , 1.4 mM CaCl 2 , 1.2 mM MgSO 4 , 10 mM d ‐glucose, and 10 mM HEPES (pH 7.4)], and the uptake was initiated by applying [ 3 H]nicotine (0.5 μCi/mL, 6 nM) dissolved in ECF buffer at 37°C in the absence or presence of inhibitors.…”