The ability of low micromolar concentrations of the polyunsaturated fatty acid, arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid) to inhibit the high-affinity, sodium-dependent transport of [3H]D-aspartate into purified synaptosomes of rat brain has been examined. Pre-incubation of the synaptosomes with arachidonic acid for 10-60 min produced a marked potentiation of the response to 10 microM arachidonic acid compared to co-incubation, and the threshold for inhibition of [3H]D-aspartate transport occurred at a concentration of 1 microM. Minimal inhibition of transport was seen with the unsaturated fatty acids, cis-oleic (cis-9-octadecenoic acid) and cis-linolenic (cis-9,12,15-octadecatrienoic acid), nor with the 20-carbon saturated fatty acid, arachidic acid (n-eicosanoic acid). Inclusion of the cyclo-oxygenase inhibitor, nor-dihydroguaretic acid (NDGA), in the presence of 5 microM arachidonic acid did not alter the inhibition of [3H]D-aspartate transport between 0-10 min, but did enhance the response at longer pre-incubation times. Inhibition of [3H]D-aspartate transport by arachidonic acid persisted during addition of the calcium ionophore, A23187, whereas removal of calcium ions from the incubation medium potentiated the response to arachidonic acid. The results are discussed in terms of the physiological relevance of the inhibition of glutamate transport by arachidonic acid, and suggest that regulation of inhibition of the glutamate transporter by arachidonic acid may be achieved by changes in the extracellular, as well as the intracellular, concentration of calcium ions.
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