6-cyano-7-nitroquinoxaline-2-3-dione and isospaglumic-acid

1. We have examined the actions and pharmacology of two putative optic nerve transmitters, N-acetylaspartylglutamate (NAAG) and L-homocysteic acid (L-HCA), in the feline dorsal lateral geniculate nucleus (dLGN). We compared the responses obtained to iontophoretic application of these substances with those elicited by visual stimulation and application of specific N-methyl-D-aspartate (NMDA) and non-NMDA receptor agonists. The relative effects of the selective NMDA antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) and the selective non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were tested on these responses. 2. There was a pronounced contrast between the influence of iontophoretically applied NAAG and L-HCA on dLGN cells. Iontophoretic application of NAAG [ejection current range 75-200 nA (mean 125 nA)] evoked either no effect (17/37), or very weak and sluggish excitatory (16/37) or inhibitory (4/37) effects. Conversely, L-HCA application [current range 25-136 nA (mean 67 nA)] elicited brisk and powerful excitatory responses (32/32) that were comparable with those produced by visual stimulation and iontophoresis of NMDA, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). 3. Responses to L-HCA were selectively antagonized by application of the NMDA receptor antagonist CPP but were generally much less affected by the non-NMDA receptor antagonist CNQX. The weak and inconsistent responses to NAAG were not compatible with an evaluation of antagonist effects. 4. CPP application at dose levels selective for NMDA with respect to kainate and AMPA did not exert equal effects on L-HCA and NMDA. Whereas the mean responses to L-HCA were reduced to 32% of control for Y cells and 21% for X cells, those to NMDA were 11 and 11%, respectively. However, the level of reduction of the visual response for X and Y cells was very similar to that of L-HCA, visual responses being reduced to 35 and 22% of control for Y and X cells. 5. CNQX application reduced the visual response level of Y cells to 64% of control and that of X cells to 65%. The mean level for the L-HCA response of Y cells was 106% of control; the mean for X cells, 79%, was substantially below control. The responses to kainate and AMPA were reduced to a much greater extent. 6. The data suggest that it is unlikely that NAAG is the optic nerve transmitter.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Cats; Dipeptides; Female; Geniculate Bodies; Homocysteine; Immunohistochemistry; Iontophoresis; Neurons; Neurotransmitter Agents; Photic Stimulation; Piperazines; Quinoxalines

1. Olfactory bulb neurons were dissociated from neonatal rats and plated at low density on a confluent layer of olfactory bulb astrocytes. Intracellular stimulation of presumptive mitral/tufted (M/T) cells evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in adjacent neurons. Whole-cell recording techniques and a flow-pipe drug delivery system were used to compare EPSPs with voltage-clamp recordings of currents evoked by excitatory amino acids (EAA) including N-acetylaspartylglutamate (NAAG), a putative mitral cell transmitter. 2. Cultured olfactory bulb neurons were morphologically and physiologically distinct. Large pyramidal-shaped neurons were present, which were NAAG immunoreactive; stimulation of these neurons invariably evoked EPSPs, suggesting that they were M/T cells. The majority of small bipolar neurons were glutamic acid decarboxylase (GAD) immunoreactive consistent with granule or periglomerular gamma-aminobutyric acid (GABA)ergic interneurons. 3. Monosynaptic EPSPs between M/T cells could be separated into fast and slow components by the use of EAA receptor antagonists. A fast component with a time-to-peak of 7.7 +/- 1.0 (SE) ms and half-width of 31.8 +/- 7.4 ms was blocked by the non-NMDA receptor antagonist 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline (CNQX, 2.5 microM). The slow component (time-to-peak = 41.4 +/- 7.2 ms; half-width = 218.9 +/- 40.4 ms) was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5, 100 microM). 4. Under voltage clamp, flow-pipe applications of NAAG (10-1,000 microM) evoked inward currents at a holding potential of -60 mV in Mg-free solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Animals, Newborn; Cells, Cultured; Dipeptides; Electrophysiology; Evoked Potentials; Neurons; Olfactory Bulb; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate; Synapses; Synaptic Transmission