PMID- 29593549
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240314
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 9
DP  - 2018
TI  - Functional Polarity of Microvascular Brain Endothelial Cells Supported by 
      Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis.
PG  - 171
LID - 10.3389/fphys.2018.00171 [doi]
LID - 171
AB  - The homeostatic regulation of large neutral amino acid (LNAA) concentration in 
      the brain interstitial fluid (ISF) is essential for proper brain function. LNAA 
      passage into the brain is primarily mediated by the complex and dynamic 
      interactions between various solute carrier (SLC) transporters expressed in the 
      neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major 
      contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated 
      trans-endothelial transport of LNAAs, however, could not be characterized 
      precisely by available in vitro and in vivo standard methods so far. To 
      circumvent these limitations, we have incorporated published in vivo data of rat 
      brain into a robust computational model of NVU-LNAA homeostasis, allowing us to 
      evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs 
      across the blood brain barrier (BBB). We show that accounting for functional 
      polarity of MBECs with either asymmetric LAT1 distribution between membranes 
      and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is 
      required to reproduce the experimentally measured brain ISF response to 
      intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of 
      these findings, we have also investigated the effect of IP administrated 
      L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and 
      neurons. Finally, the computational model was shown to explain the 
      trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with 
      a competitive LAT1 inhibitor.
FAU - Taslimifar, Mehdi
AU  - Taslimifar M
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Epithelial Transport Group, Institute of Physiology, University of Zurich, 
      Zurich, Switzerland.
FAU - Buoso, Stefano
AU  - Buoso S
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Institute for Diagnostic and Interventional Radiology, Zurich University 
      Hospital, Zurich, Switzerland.
FAU - Verrey, Francois
AU  - Verrey F
AD  - Epithelial Transport Group, Institute of Physiology, University of Zurich, 
      Zurich, Switzerland.
AD  - Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - National Center of Competence in Research, Kidney.CH, Zurich, Switzerland.
FAU - Kurtcuoglu, Vartan
AU  - Kurtcuoglu V
AD  - The Interface Group, Institute of Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, 
      Switzerland.
AD  - National Center of Competence in Research, Kidney.CH, Zurich, Switzerland.
AD  - Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20180313
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC5859092
OTO - NOTNLM
OT  - SLC7A5/LAT1
OT  - amino acid transporter
OT  - blood brain barrier
OT  - large neutral amino acid
OT  - neurovascular unit
EDAT- 2018/03/30 06:00
MHDA- 2018/03/30 06:01
PMCR- 2018/03/13
CRDT- 2018/03/30 06:00
PHST- 2017/11/16 00:00 [received]
PHST- 2018/02/20 00:00 [accepted]
PHST- 2018/03/30 06:00 [entrez]
PHST- 2018/03/30 06:00 [pubmed]
PHST- 2018/03/30 06:01 [medline]
PHST- 2018/03/13 00:00 [pmc-release]
AID - 10.3389/fphys.2018.00171 [doi]
PST - epublish
SO  - Front Physiol. 2018 Mar 13;9:171. doi: 10.3389/fphys.2018.00171. eCollection 
      2018.