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Glutamate‐Induced 45 Ca 2+ Uptake into Immature Cerebral Cortex Neurons Shows a Distinct Pharmacological Profile
Author(s) -
Frandsen Aase,
Drejer Jørgen,
Schousboe Arne
Publication year - 1989
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.1471-4159.1989.tb09268.x
Subject(s) - glutamate receptor , nmda receptor , agonist , chemistry , cerebral cortex , metabotropic glutamate receptor , biophysics , excitatory postsynaptic potential , biochemistry , neuroscience , medicine , endocrinology , receptor , biology
Abstract: Glutamate‐induced 45 Ca 2+ uptake was studied in cerebral cortex neurons cultured for 4 days, i.e., at a developmental stage where the neurons are sensitive to the mixed agonist glutamate but not to the actions of N ‐methyl‐D‐aspartate or other excitatory amino acids. Using this experimental approach, allowing the investigation of effects elicited only by glutamate, it was demonstrated that the glutamate‐stimulated Ca 2+ influx could be completely antagonized by MK‐801, phencyclidine, and cyclazocine in the nanomolar range, and by 3‐(2‐carboxypiperazin‐4‐yl)propyl‐l‐phosphonate and D‐2‐amino‐5‐phosphonopentanoate (APV) in the low micromolar range. However, the glutamate response was unaffected by variations in the Mg 2+ concentration in the exposure media. In addition, the two qui‐noxalinediones 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione and 6,7‐dini‐troquinoxaline‐2,3‐dione were equipotent with APV in blocking the glutamate‐stimulated Ca 2+ uptake. PK 26124 blocked the response in the high micromolar concentration range. Ketamine and γ‐glu‐tamylaminomethylsulfonate were essentially without effect at concentrations up to 10 μ M and 300 μ M , respectively. These results may suggest the existence of a glutamate receptor with a pharmacological profile not compatible with the existent classification of glutamate receptor subtypes.