{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:27:47Z","timestamp":1790706467568,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,5,19]],"date-time":"2011-05-19T00:00:00Z","timestamp":1305763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:sec><jats:label\/><jats:p> <jats:italic>J. Neurochem.<\/jats:italic> (2011) 10.1111\/j.1471\u20104159.2011.07289.x<\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>In our previous work, we found that perfusion of the rat cerebral cortex with hypo\u2010osmotic medium triggers massive release of the excitatory amino acid L\u2010glutamate but decreases extracellular levels of L\u2010glutamine (R. E. Haskew\u2010Layton <jats:italic>et\u00a0al.<\/jats:italic>, PLoS ONE, 3: e3543). The release of glutamate was linked to activation of volume\u2010regulated anion channels, whereas mechanism(s) responsible for alterations in extracellular glutamine remained unclear. When mannitol was added to the hypo\u2010osmotic medium to reverse reductions in osmolarity, changes in microdialysate levels of glutamine were prevented, indicating an involvement of cellular swelling. As the main source of brain glutamine is astrocytic synthesis and export, we explored the impact of hypo\u2010osmotic medium on glutamine synthesis and transport in rat primary astrocyte cultures. In astrocytes, a 40% reduction in medium osmolarity moderately stimulated the release of L\u2010[<jats:sup>3<\/jats:sup>H]glutamine by \u223ctwofold and produced no changes in L\u2010[<jats:sup>3<\/jats:sup>H]glutamine uptake. In comparison, hypo\u2010osmotic medium stimulated the release of glutamate (traced with D\u2010[<jats:sup>3<\/jats:sup>H]aspartate) by more than 20\u2010fold. In whole\u2010cell enzymatic assays, we discovered that hypo\u2010osmotic medium caused a 20% inhibition of astrocytic conversion of L\u2010[<jats:sup>3<\/jats:sup>H]glutamate into L\u2010[<jats:sup>3<\/jats:sup>H]glutamine by glutamine synthetase. Using an HPLC assay, we further found a 35% reduction in intracellular levels of endogenous glutamine. Overall, our findings suggest that cellular swelling (i) inhibits astrocytic glutamine synthetase activity, and (ii) reduces substrate availability for this enzyme because of the activation of volume\u2010regulated anion channels. These combined effects likely lead to reductions in astrocytic glutamine export <jats:italic>in vivo<\/jats:italic> and may partially explain occurrence of hyperexcitability and seizures in human hyponatremia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1471-4159.2011.07289.x","type":"journal-article","created":{"date-parts":[[2011,4,23]],"date-time":"2011-04-23T05:36:26Z","timestamp":1303536986000},"page":"140-152","source":"Crossref","is-referenced-by-count":26,"title":["Hypo\u2010osmotic swelling modifies glutamate\u2010glutamine cycle in the cerebral cortex and in astrocyte cultures"],"prefix":"10.1111","volume":"118","author":[{"given":"Mar\u00eda C.","family":"Hyzinski\u2010Garc\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie Y.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e 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