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NH<jats:sub>4<\/jats:sub>Cl (5 mmol\/L) and hypoosmotic exposure (205 mosmol\/L) induced a rapid colchicine\u2010sensitive loss of cellular glutamate and glutamate appearance in the extracellular space. The NH<jats:sub>4<\/jats:sub>Cl\u2010induced glutamate loss from astrocytes was strongly blunted after transfection of the cells with VAMP2 siRNA. Ammonia\u2010induced exocytosis of VAMP2\u2010YFP expressing vesicles was shown by total internal reflection fluorescence microscopy (TIRF\u2010M). Glutamate exocytosis in response to ammonia was sensitive to chelation of Ca<jats:sup>2+<\/jats:sup>, cyclooxygenase inhibition by indomethacin and colchicine. Ammonia triggered the rapid formation of prostanoids, which were identified as upstream events in ammonia\u2010induced glutamate exocytosis. Also, addition of prostaglandin E<jats:sub>2<\/jats:sub> or of tumor necrosis factor (TNF)\u2010\u03b1 triggered glutamate exocytosis. Inhibition of ammonia\u2010induced glutamate exocytosis after transfection of VAMP2 siRNA inhibited ammonia\u2010induced RNA oxidation. It is concluded that ammonia triggers a prostanoid\u2010 and Ca<jats:sup>2+<\/jats:sup>\u2010dependent glutamate exocytosis, which is essential for induction of ammonia\u2010induced RNA oxidation. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20955","type":"journal-article","created":{"date-parts":[[2009,12,14]],"date-time":"2009-12-14T18:37:17Z","timestamp":1260815837000},"page":"691-705","source":"Crossref","is-referenced-by-count":51,"title":["Ammonia triggers exocytotic release of <scp>L<\/scp>\u2010glutamate from cultured rat 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