Glutamate stimulates ascorbate transport by astrocytes

The concentrations of glutamate and ascorbate in brain extracellular fluid increase following seizure activity, trauma and ischemia. Extracellular asc orbate concentration also rises following intracerebral glutamate injection . We hypothesized that glutamate triggers the release of ascorbate from ast rocytes. We observed in primary cultures of rat cerebral astrocytes that gl utamate increased ascorbate efflux significantly within 30 min. The half-ma ximal effective concentration of glutamate was 180 +/- 30 mu M. Glutamate-s timulated efflux of ascorbate was attenuated by hypertonic media. 4,4'-diis othiocyanatostilbene-2,2'-disulfonic acid inhibited both Na+-dependent glut amate uptake and ascorbate efflux. Two other inhibitors of volume-sensitive organic anion channels (1,9-dideoxyforskolin and 5-nitro-2-(3-phenylpropyl amino) benzoic acid) did not slow glutamate uptake but prevented stimulatio n of ascorbate efflux. Glutamate also stimulated the uptake of ascorbate by ascorbate-depleted astrocytes. In contrast, glutamate uptake was not affec ted by intracellular ascorbate, thus ruling out a putative glutamate-ascorb ate heteroexchange mechanism. These results are consistent with activation by glutamate of ascorbate-permeant channels in astrocytes. (C) 2000 Elsevie r Science B.V. All rights reserved.