Excitatory amino acid-induced release of 3H-GABA from cultured mouse cerebral cortex interneurons.
A newly developed continuous superfusion model was used for studies of 3H-GABA release from cultured mouse cerebral cortex neurons. It was found that a series of excitatory amino acids (EAAs) representing all receptor subtypes evoked Ca2+- dependent release of 3H-GABA from the neurons. Quisqualate was the most potent agonist tested, with an EC50 value of 75 nM. L-Glutamate, N-methyl-D-aspartate (NMDA), and kainate showed EC50 values of 12, 16 and 29 microM, respectively. The EAA-evoked 3H-GABA release could be blocked by a series of EAA antagonists. The highly selective NMDA antagonist D-2-amino-5-phosphonovaleric acid (D-APV) was found to block NMDA responses, whereas the nonselective antagonists cis-2,3-piperidine dicarboxylic acid (PDA) and gamma-D-glutamyl-aminomethyl sulphonic acid (GAMS) blocked responses to all agonists. NMDA responses were found to be sensitive to Mg+ blockade. EAA- as well as potassium-induced 3H-GABA release from the neurons could be detected as early as day 5 in culture. However, during the culture period up to 12 d, the responses to K+, quisqualate, and NMDA were increased. The ontogenetic development of binding sites for quisqualate, kainate, and NMDA in mouse cortex was studied using the radioligands 3H-alpha-amino-3-hydroxy-5-methyl-4-isoxasole propionate (3H-AMPA), 3H-kainate, and 3H-L-glutamate, respectively. The development of binding sites for the different EAA-receptor subtypes showed a good correlation with the development of neuronal 3H-GABA release evoked by the excitatory amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)
D015763:2-Amino-5-phosphonovalerate; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001665:Binding Sites; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010069:Oxadiazoles / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D016318:Quisqualic Acid; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D010069:Oxadiazoles; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D014633:Valine; D011188:Potassium; D007608:Kainic Acid