Differential Modulation of Human Glutamate Transporter Subtypes by Arachidonic Acid

Arachidonic acid has been proposed to be a messenger molecule released following synaptic activation of glutamate receptors and during ischemia. Here we demonstrate that micromolar levels of arachidonic acid inhibit glutamate uptake mediated by EAAT1, a human excitatory amino acid transporter widely...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-03, Vol.270 (12), p.6433-6435
Main Authors: Zerangue, N, Arriza, J L, Amara, S G, Kavanaugh, M P
Format: Article
Language:English
Subjects:
Amino Acid Transport System X-AG
Animals
Arachidonic Acid - pharmacology
ATP-Binding Cassette Transporters - drug effects
Biological Transport - drug effects
Dose-Response Relationship, Drug
Female
Glutamic Acid - metabolism
Humans
Xenopus
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Summary:Arachidonic acid has been proposed to be a messenger molecule released following synaptic activation of glutamate receptors and during ischemia. Here we demonstrate that micromolar levels of arachidonic acid inhibit glutamate uptake mediated by EAAT1, a human excitatory amino acid transporter widely expressed in brain and cerebellum, by reducing the maximal transport rate approximately 30%. In contrast, arachidonic acid increased transport mediated by EAAT2, a subtype abundantly expressed in forebrain and midbrain, by causing the apparent affinity for glutamate to increase more than 2-fold. The results demonstrate that the response of different glutamate transporter subtypes to arachidonic acid could influence synaptic transmission and modulate excitotoxicity via positive or negative feedback according to the transporter(s) present in a particular region.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.12.6433