| Involvement of system A in the retina-to-blood transport of l-proline across the inner blood-retinal barrier. | |
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MedLine Citation:
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PMID: 20074566 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of the present study was to elucidate the mechanisms of retina-to-blood transport of l-proline across the blood-retinal barrier (BRB) in vivo and in vitro, and to identify the responsible transporter(s). The vitreous humor/retina-to-blood transport of [(3)H]l-proline across the BRB was evaluated by microdialysis. Transport mechanisms of [(3)H]l-proline were investigated by cellular uptake using an in vitro model of the inner BRB (TR-iBRB2 cells). The mRNA level of system A was determined by quantitative real-time PCR analysis with specific primers. [(3)H]l-Proline and [(14)C]d-mannitol, which is a bulk flow marker, were bi-exponentially eliminated from the vitreous humor after vitreous bolus injection. The elimination rate constant of [(3)H]l-proline during the terminal phase was 1.6-fold greater than that of [(14)C]d-mannitol. The terminal elimination rate constant difference between [(3)H]l-proline and [(14)C]d-mannitol was reduced in the retinal presence of 3 mM l-proline and 5 mM alpha-methylaminoisobutyric acid, suggesting that l-proline is transported via a carrier-mediated retina-to-blood transport process across the BRB. [(3)H]l-Proline uptake by TR-iBRB2 cells appeared to be mediated through a saturable and Na(+)-dependent process. The corresponding Michaelis-Menten constant was 392 muM. This process was reduced by substrates for system A, suggesting that system A is involved in l-proline uptake. Of the isoforms of system A, ATA1, ATA2, and ATA3, ATA2 mRNA is predominantly expressed in TR-iBRB2 cells and isolated rat retinal endothelial cells. In conclusion, system A, most likely ATA2, is responsible for the retina-to-blood transport of l-proline across the inner BRB and may play a role in maintaining the concentration of small neutral amino acids in the retina. |
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Authors:
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Daisuke Yoneyama; Yumiko Shinozaki; Wan-Liang Lu; Masatoshi Tomi; Masanori Tachikawa; Ken-Ichi Hosoya |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-13 |
Journal Detail:
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Title: Experimental eye research Volume: 90 ISSN: 1096-0007 ISO Abbreviation: Exp. Eye Res. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-26 Completed Date: 2010-04-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370707 Medline TA: Exp Eye Res Country: England |
Other Details:
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Languages: eng Pagination: 507-13 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport System A
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genetics,
metabolism* Animals Biological Transport Blood / metabolism* Blood-Retinal Barrier / metabolism* Capillaries Cell Culture Techniques Endothelium, Vascular / metabolism* Male Microdialysis Proline / metabolism* RNA, Messenger / metabolism Rats Rats, Transgenic Rats, Wistar Retina / metabolism* Retinal Vessels / cytology Reverse Transcriptase Polymerase Chain Reaction Time Factors Vitreous Body / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Transport System A; 0/RNA, Messenger; 147-85-3/Proline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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