Glutamate-induced 45Ca2+ uptake into immature cerebral cortex neurons shows a distinct pharmacological profile.
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 microM and 300 microM, 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.
Frandsen
A
A
PharmaBiotec Research Center, Department of Biochemistry A, University of Copenhagen, Denmark.
Drejer
J
J
Schousboe
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011865:Radioisotope Dilution Technique
D002132:Calcium Radioisotopes; D005971:Glutamates; D018698:Glutamic Acid; D008274:Magnesium; D002118:Calcium