Glutamate, kainate and quisqualate enhance GABA-dependent chloride uptake in cortex.
Several lines of evidence indicate a possible interaction between the major inhibitory and excitatory cortical neurotransmitters, GABA and glutamate. To assess the neurochemical basis for such an interaction, we examined the effects of glutamate and several analogs on GABA-dependent chloride uptake in a mouse cortical synaptoneurosome preparation. L-Glutamate and the specific receptor subtype ligands kainate and quisqualate led to a small but significant enhancement in chloride uptake in the presence, but not the absence, of the GABA analog muscimol (5 microM). Enhancement was seen at excitatory amino acid (EAA) concentrations of 2-10 microM, but not at higher concentrations. D-Glutamate, NMDA, the NMDA-related antagonists APV and MK801, and the kainate/quisqualate antagonist CNQX, had no effect on chloride uptake. However, CNQX (50 microM) but not APV (50 microM) blocked the increase in chloride uptake due to kainate or quisqualate (10 microM). In addition, depolarization of synaptoneurosomes using high potassium (40 mM KC1) or ouabain pretreatment (5 microM) blocked the effects of kainate and quisqualate. Glutamate, kainate, and quisqualate had no effect on binding at the benzodiazepine, TBPS, or GABA sites on the GABAA receptor complex.
Department of Psychiatry, Tufts University School of Medicine, Boston, MA.
A
A
Schatzki
M
M
McMillian
L G
LG
Miller
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018118:Chloride Channels; D002712:Chlorides; D005971:Glutamates; D007473:Ion Channels; D008565:Membrane Proteins; D011810:Quinoxalines; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D007608:Kainic Acid