ABSTRACT

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.

FOOTNOTES

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This work was supported by National Institutes of Health Grant GM48709. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked ``advertisement'' in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§

To whom correspondence should be addressed: Vollum Inst., Oregon Health Sciences University, 3181 SW Sam Jackson Pk. Rd., Portland, OR 97201. Tel.: 503-494-4601; Fax: 503-494-2285; kavanaug{at}ohsu.edu.

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The abbreviation used is: EAAT1, EAAT2, EAAT3, human excitatory amino acid transporters 1-3.

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N. Zerangue, J. Arriza, S. Amara, and M. Kavanaugh, unpublished results.

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