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 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.
Zerangue
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Vollum Institute, Oregon Health Sciences University, Portland 97201.
Arriza
J L
JL
Amara
S G
SG
Kavanaugh
M P
MP
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D014981:Xenopus
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D016718:Arachidonic Acid; D018698:Glutamic Acid