| Effect of pluronic p85 on amino acid transport in bovine brain microvessel endothelial cells. | |
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MedLine Citation:
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PMID: 18677571 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A synthetic amphiphilic block copolymer Pluronic P85 (P85) was shown to be among the most potent inhibitors of Pgp efflux system in the blood-brain barrier (BBB) and capable of enhancing delivery of Pgp substrates to the brain. The purpose of this work is to evaluate the effects of P85 on amino acid transport in BBB. Primary bovine brain microvessel endothelial cells (BBMEC) grown on membrane inserts were used as an in vitro BBB model. Expression of amino acid transporters, like large neutral amino acid transporter 1, cationic amino acid transporter 1, and small neutral amino acid transporter 1, were confirmed by reverse transcriptase polymerase chain reaction. Effects of P85 on amino acid transporters were examined using their substrates: (3)H-phenylalanine, (3)H-lysine, and (3)H-methylaminoisobutyric acid, respectively. BBMEC permeability studies were carried out in apical (AP) to basolateral (BL) and BL to AP directions. P85 added at the AP side had little, if any, effect on AP to BL ("blood to brain") transport for all examined amino acids in BBMEC monolayers. However, 0.1% P85 added at the BL side significantly increased the BL to AP transport of these substrates. Furthermore, the effective concentrations of P85 were also shown to induce plasma membrane depolarization and increase intracellular sodium concentration in BBMEC, which can contribute to the effects of the copolymer on the energy-dependent transport systems. All together, despite profound effects on transport system(s) at the brain side of cell monolayers, P85 had no effect on AP to BL transport of amino acids in brain microvessel endothelial cell model. |
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Authors:
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Xiaobin Zhang; Daria Y Alakhova; Elena V Batrakova; Shu Li; Zhihui Yang; Yili Li; Alexander V Kabanov |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-08-02 |
Journal Detail:
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Title: Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology Volume: 4 ISSN: 1557-1904 ISO Abbreviation: J Neuroimmune Pharmacol Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-17 Completed Date: 2009-05-11 Revised Date: 2013-06-05 |
Medline Journal Info:
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Nlm Unique ID: 101256586 Medline TA: J Neuroimmune Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 35-46 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Transport Systems
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metabolism* Amino Acids / metabolism* Animals Biological Transport, Active / drug effects Brain Chemistry / drug effects* Capillaries / cytology, drug effects, metabolism Cattle Cell Separation Cells, Cultured Endothelial Cells / drug effects, metabolism* Membrane Potentials / drug effects Microscopy, Confocal P-Glycoprotein / metabolism Poloxalene / pharmacology* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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NS36229/NS/NINDS NIH HHS; R01 NS036229-05A2/NS/NINDS NIH HHS; R01 NS036229-06/NS/NINDS NIH HHS; R01 NS036229-07/NS/NINDS NIH HHS; R01 NS036229-08/NS/NINDS NIH HHS; R01 NS036229-09/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Transport Systems; 0/Amino Acids; 0/P-Glycoprotein; 0/pluronic block copolymer p85; 9003-11-6/Poloxalene |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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