Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model

Research output: Contribution to journalJournal articlepeer-review

Standard

Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model. / Helms, Hans Cc; Aldana, Blanca I; Groth, Simon; Jensen, Morten M; Waagepetersen, Helle S; Nielsen, Carsten U; Brodin, Birger.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 37, No. 12, 2017, p. 3744–3758.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Helms, HC, Aldana, BI, Groth, S, Jensen, MM, Waagepetersen, HS, Nielsen, CU & Brodin, B 2017, 'Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model', Journal of Cerebral Blood Flow and Metabolism, vol. 37, no. 12, pp. 3744–3758. https://doi.org/10.1177/0271678X17690760

APA

Helms, H. C., Aldana, B. I., Groth, S., Jensen, M. M., Waagepetersen, H. S., Nielsen, C. U., & Brodin, B. (2017). Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model. Journal of Cerebral Blood Flow and Metabolism, 37(12), 3744–3758. https://doi.org/10.1177/0271678X17690760

Vancouver

Helms HC, Aldana BI, Groth S, Jensen MM, Waagepetersen HS, Nielsen CU et al. Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model. Journal of Cerebral Blood Flow and Metabolism. 2017;37(12):3744–3758. https://doi.org/10.1177/0271678X17690760

Author

Helms, Hans Cc ; Aldana, Blanca I ; Groth, Simon ; Jensen, Morten M ; Waagepetersen, Helle S ; Nielsen, Carsten U ; Brodin, Birger. / Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model. In: Journal of Cerebral Blood Flow and Metabolism. 2017 ; Vol. 37, No. 12. pp. 3744–3758.

Bibtex

@article{4c58e94fdd854d92b21c2eaa0a48e648,
title = "Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model",
abstract = "The aim was to characterize the clearance pathways for L-glutamate from the brain interstitial fluid across the blood-brain barrier using a primary in vitro bovine endothelial/rat astrocyte co-culture. Transporter profiling was performed using uptake studies of radiolabeled L-glutamate with co-application of transporter inhibitors and competing amino acids. Endothelial abluminal L-glutamate uptake was almost abolished by co-application of an EAAT-1 specific inhibitor, whereas luminal uptake was inhibited by L-glutamate and L-aspartate (1 mM). L-glutamate uptake followed Michaelis-Menten-like kinetics with high and low affinity at the abluminal and luminal membrane, respectively. This indicated that L-glutamate is taken up via EAAT-1 at the abluminal membrane and exits at the luminal membrane via a low affinity glutamate/aspartate transporter. Metabolism of L-glutamate and transport of metabolites was examined using [U-(13)C] L-glutamate. Intact L-glutamate and metabolites derived from oxidative metabolism were transported through the endothelial cells. High amounts of L-glutamate-derived lactate in the luminal medium indicated cataplerosis via malic enzyme. Thus, L-glutamate can be transported intact from brain to blood via the concerted action of abluminal and luminal transport proteins, but the total brain clearance is highly dependent on metabolism in astrocytes and endothelial cells followed by transport of metabolites.",
author = "Helms, {Hans Cc} and Aldana, {Blanca I} and Simon Groth and Jensen, {Morten M} and Waagepetersen, {Helle S} and Nielsen, {Carsten U} and Birger Brodin",
year = "2017",
doi = "10.1177/0271678X17690760",
language = "English",
volume = "37",
pages = "3744–3758",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "SAGE Publications",
number = "12",

}

RIS

TY - JOUR

T1 - Characterization of the L-glutamate clearance pathways across the blood-brain barrier and the effect of astrocytes in an in vitro blood-brain barrier model

AU - Helms, Hans Cc

AU - Aldana, Blanca I

AU - Groth, Simon

AU - Jensen, Morten M

AU - Waagepetersen, Helle S

AU - Nielsen, Carsten U

AU - Brodin, Birger

PY - 2017

Y1 - 2017

N2 - The aim was to characterize the clearance pathways for L-glutamate from the brain interstitial fluid across the blood-brain barrier using a primary in vitro bovine endothelial/rat astrocyte co-culture. Transporter profiling was performed using uptake studies of radiolabeled L-glutamate with co-application of transporter inhibitors and competing amino acids. Endothelial abluminal L-glutamate uptake was almost abolished by co-application of an EAAT-1 specific inhibitor, whereas luminal uptake was inhibited by L-glutamate and L-aspartate (1 mM). L-glutamate uptake followed Michaelis-Menten-like kinetics with high and low affinity at the abluminal and luminal membrane, respectively. This indicated that L-glutamate is taken up via EAAT-1 at the abluminal membrane and exits at the luminal membrane via a low affinity glutamate/aspartate transporter. Metabolism of L-glutamate and transport of metabolites was examined using [U-(13)C] L-glutamate. Intact L-glutamate and metabolites derived from oxidative metabolism were transported through the endothelial cells. High amounts of L-glutamate-derived lactate in the luminal medium indicated cataplerosis via malic enzyme. Thus, L-glutamate can be transported intact from brain to blood via the concerted action of abluminal and luminal transport proteins, but the total brain clearance is highly dependent on metabolism in astrocytes and endothelial cells followed by transport of metabolites.

AB - The aim was to characterize the clearance pathways for L-glutamate from the brain interstitial fluid across the blood-brain barrier using a primary in vitro bovine endothelial/rat astrocyte co-culture. Transporter profiling was performed using uptake studies of radiolabeled L-glutamate with co-application of transporter inhibitors and competing amino acids. Endothelial abluminal L-glutamate uptake was almost abolished by co-application of an EAAT-1 specific inhibitor, whereas luminal uptake was inhibited by L-glutamate and L-aspartate (1 mM). L-glutamate uptake followed Michaelis-Menten-like kinetics with high and low affinity at the abluminal and luminal membrane, respectively. This indicated that L-glutamate is taken up via EAAT-1 at the abluminal membrane and exits at the luminal membrane via a low affinity glutamate/aspartate transporter. Metabolism of L-glutamate and transport of metabolites was examined using [U-(13)C] L-glutamate. Intact L-glutamate and metabolites derived from oxidative metabolism were transported through the endothelial cells. High amounts of L-glutamate-derived lactate in the luminal medium indicated cataplerosis via malic enzyme. Thus, L-glutamate can be transported intact from brain to blood via the concerted action of abluminal and luminal transport proteins, but the total brain clearance is highly dependent on metabolism in astrocytes and endothelial cells followed by transport of metabolites.

U2 - 10.1177/0271678X17690760

DO - 10.1177/0271678X17690760

M3 - Journal article

C2 - 28145808

VL - 37

SP - 3744

EP - 3758

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 12

ER -

ID: 173155178