REGULATION OF GLUTAMATE IN CULTURES OF HUMAN MONOCYTIC THP-1 AND ASTROCYTOMA U-373 MG CELLS

Glutamate, an excitatory neurotransmitter, is neurotoxic at high conce ntrations. Neuroglial cells, including astrocytes and microglia, play an important role in regulating its extracellular levels. Cultured hum an monocytic THP-1 cells increased their glutamate secretion following 18 and 68 h exposure to the inflammatory mediators zymosan, phorbol m yristate acetate (PMA), lipopolysaccharide, interferon-gamma, tumor-ne crosis factor-alpha and interleukin-1 beta. Cultured astrocytoma U-373 MG cells increased their glutamate secretion following similar exposu re to zymosan and PMA. DL-alpha-aminopimelic acid, an inhibitor of the glutamate secretion system, reduced extracellular glutamate in both c ell culture systems, while the high-affinity glutamate uptake inhibito rs D-Aspartic acid, DL-threo-beta-hydroxyaspartic acid and L-trans-pyr rolidine-2,4-dicarboxylic acid increased extracellular glutamate in U- 373 MG, but not THP-1 cell cultures. In co-cultures of THP-I and U-373 MG cells, extracellular glutamate levels were increased significantly by the Alzheimer beta-amyloid peptide (1-40) and were decreased signi ficantly by the anti-inflammatory drug dexamethasone. These data indic ate that inflammatory stimuli may increase extracellular glutamate whi le antiinflammatory drugs decrease it. (C) 1997 Elsevier Science B.V.