Glutamate-Induced45Ca2+Uptake into Immature Cerebral Cortex Neurons Shows a Distinct Pharmacological Profile

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Abstract
Glutamate-induced 45Ca2+ 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 Ca2+ influx could be completely antagonized by MK-801, phencyclidine, and cyclazocine in the nanomolar range, and by 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate and D-2-amino-5-phosphonopentanoate (APV) in the low micromolar range. However, the glutamate response was unaffected by variations in the Mg2+ concentration in the exposure media. In addition, the two quinoxalinediones 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2-3-dione were equipotent with APV in blocking the glutamate-stimulated Ca2+ uptake. PK 26124 blocked the response in the high micromolar concentration range. Ketamine and .gamma.-glutamylaminomethylsulfonate were essentially without effect at concentrations up to 10 .mu.M and 300 .mu.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.

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