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ATP stimulates calcium‐dependent glutamate release from cultured astrocytes
Author(s) -
Jeremic Aleksandar,
Jeftinija Ksenija,
Stevanovic Jelena,
Glavaski Aleksandra,
Jeftinija Srdija
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00272.x
Subject(s) - glutamate receptor , calcium , egta , thapsigargin , calcium in biology , extracellular , intracellular , metabotropic glutamate receptor , chemistry , biology , biochemistry , biophysics , receptor , organic chemistry
ATP caused a dose‐dependent, receptor‐mediated increase in the release of glutamate and aspartate from cultured astrocytes. Using calcium imaging in combination HPLC we found that the increase in intracellular calcium coincided with an increase in glutamate and aspartate release. Competitive antagonists of P 2 receptors blocked the response to ATP. The increase in intracellular calcium and release of glutamate evoked by ATP were not abolished in low Ca 2+ ‐EGTA saline, suggesting the involvement of intracellular calcium stores. Pre‐treatment of glial cultures with an intracellular Ca 2+ chelator abolished the stimulatory effects of ATP. Thapsigargin (1 µ m ), an inhibitor of Ca 2+ ‐ATPase from the Ca 2+ pump of internal stores, significantly reduced the calcium transients and the release of aspartate and glutamate evoked by ATP. U73122 (10 µ m ), a phospholipase C inhibitor, attenuated the ATP‐stimulatory effect on calcium transients and blocked ATP‐evoked glutamate release in astrocytes. Replacement of extracellular sodium with choline failed to influence ATP‐induced glutamate release. Furthermore, inhibition of the glutamate transporters p ‐chloromercuri‐phenylsulfonic acid and l trans‐ pyrolidine‐2,4‐dicarboxylate failed to impair the ability of ATP to stimulate glutamate release from astrocytes. However, an anion transport inhibitor, furosemide, and a potent Cl − channel blocker, 5‐nitro‐2(3‐phenylpropylamino)‐benzoate, reduced ATP‐induced glutamate release. These results suggest that ATP stimulates excitatory amino acid release from astrocytes via a calcium‐dependent anion‐transport sensitive mechanism.