title: Regulation of glutamate in cultures of human monocytic THP-1 and astrocytoma U-373 MG cells.
abstract: Glutamate, an excitatory neurotransmitter, is neurotoxic at high concentrations. Neuroglial cells, including astrocytes and microglia, play an important role in regulating its extracellular levels. Cultured human monocytic THP-1 cells increased their glutamate secretion following 18 and 68 h exposure to the inflammatory mediators zymosan, phorbol myristate acetate (PMA), lipopolysaccharide, interferon-gamma, tumor-necrosis factor-alpha and interleukin-1beta. Cultured astrocytoma U-373 MG cells increased their glutamate secretion following similar exposure to zymosan and PMA. DL-Alpha-aminopimelic acid, an inhibitor of the glutamate secretion system, reduced extracellular glutamate in both cell culture systems, while the high-affinity glutamate uptake inhibitors D-Aspartic acid, DL-threo-beta-hydroxyaspartic acid and L-trans-pyrrolidine-2,4-dicarboxylic acid increased extracellular glutamate in U-373 MG, but not THP-1 cell cultures. In co-cultures of THP-1 and U-373 MG cells, extracellular glutamate levels were increased significantly by the Alzheimer beta-amyloid peptide (1-40) and were decreased significantly by the anti-inflammatory drug dexamethasone. These data indicate that inflammatory stimuli may increase extracellular glutamate while antiinflammatory drugs decrease it.
authors.affiliation: Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada. kinsmen@unixg.ubc.ca
authors.forename: A
authors.initials: A
authors.lastname: Klegeris
authors.forename: D G
authors.initials: DG
authors.lastname: Walker
authors.forename: P L
authors.initials: PL
authors.lastname: McGeer
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010867:Pimelic Acids / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D018691:Excitatory Amino Acid Antagonists; D018836:Inflammation Mediators; D010446:Peptide Fragments; D010867:Pimelic Acids; C078592:amyloid beta-protein (1-40); C009845:alpha-aminopimelic acid; D018698:Glutamic Acid; D003907:Dexamethasone