Glutamate-induced calcium responses in rat primary cortical cultures are potentiated by co-administration of glutamate transport inhibitors.
The effects of glutamate uptake inhibitors on the L-glutamate-induced increase in intracellular calcium concentrations were assessed in rat primary cortical cultures. The glutamate (10 microM)-induced rise in intracellular calcium concentrations was strongly and dose dependently increased and prolonged by simultaneous administration of micromolar concentrations of the reference glutamate transport inhibitors, L-trans-pyrrolidine-2,4-dicarboxylate (PDC) and D- or L-threo-beta-hydroxyaspartate. PDC in concentrations up to 10 microM showed no effect on intracellular calcium when administered alone. The anticancer drug tamoxifen, which was found to be effective as a glutamate transport inhibitor, did not increase but prolonged the cellular calcium response to glutamate, indicating that it had a different mechanism of action compared to that of standard glutamate transport inhibitors. The findings suggest that compounds which inhibit the glutamate transporter may potentiate the excitatory glutamatergic signal of cultured neurons when administered together with glutamate.
Freund
W D
WD
Institute for Neurobiology, Troponwerke GmbH & Co. KG, Köln, Germany.
Grieshop
B
B
Neumann
U
U
Reddig
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors
D003998:Dicarboxylic Acids; D005971:Glutamates; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D013629:Tamoxifen; C083486:pyrrolidine-2,4-dicarboxylic acid; D002118:Calcium