Premium
Effect of ammonia on astrocytic glutamate uptake/release mechanisms
Author(s) -
Rose Christopher
Publication year - 2006
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 - 10.1111/j.1471-4159.2006.03796.x
Subject(s) - glutamate receptor , astrocyte , extracellular , intracellular , glutamate aspartate transporter , biochemistry , biology , transporter , chemistry , biophysics , microbiology and biotechnology , metabotropic glutamate receptor , neuroscience , central nervous system , receptor , gene
Hyperammonemic disorders such as acute liver failure (ALF) or urea cycle enzymopathies are associated with hyperexcitability, seizures, brain edema and increased extracellular brain glutamate. Mechanisms responsible for increased glutamate content in the extracellular space of the brain include decreased uptake by perineuronal astrocytes and/or increased release from neurons and/or astrocytes. Exposure of astrocytes to millimolar concentrations of ammonia results in cell swelling, loss of expression of the glutamate transporters excitatory amino acid transporter (EAAT‐1) and EAAT‐2 and increased release of glutamate. Three distinct mechanisms are theoretically possible to explain ammonia‐induced glutamate release from astrocytes namely: release due to swelling; reversal of glutamate transporters and due to Ca 2+ ‐dependent vesicular release. Recent identification of vesicular docking and fusion proteins in astrocytes together with glutamate‐release (due to intracellular alkanization and mobilization of intracellular Ca 2+ ‐stores) studies implies that vesicular release is a predominant mechanism responsible for ammonia‐induced release of glutamate from astrocytes.