Document Detail


Effect of pluronic p85 on amino acid transport in bovine brain microvessel endothelial cells.
MedLine Citation:
PMID:  18677571     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Xiaobin Zhang; Daria Y Alakhova; Elena V Batrakova; Shu Li; Zhihui Yang; Yili Li; Alexander V Kabanov
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-08-02
Journal Detail:
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:
Created Date:  2009-02-17     Completed Date:  2009-05-11     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  101256586     Medline TA:  J Neuroimmune Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35-46     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Sciences and Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems / 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:
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:
0/Amino Acid Transport Systems; 0/Amino Acids; 0/P-Glycoprotein; 0/pluronic block copolymer p85; 9003-11-6/Poloxalene
Comments/Corrections

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