DCG-IV inhibits synaptic transmission by activation of NMDA receptors in area CA1 of rat hippocampus.
We investigated the synaptic depressant action of the metabotropic glutamate receptor group II agonist, (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG-IV), in area CA1 of rat hippocampus. A brief bath application of DCG-IV (10 microM) caused a rapidly reversible depression to 0.57 +/- 0.22 (i.e., 43%) of baseline excitatory postsynaptic potential (epsp) slope. This depression could not be attenuated by the metabotropic glutamate receptor antagonists alpha-methyl-L-CCGI/(2S,3S,4S)-2-methyl-2-(carboxycyclopropyl++ +)glycine (MCCG), (RS)-alpha-methyl-4-tetrazolyphenylglycine (MTPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid alpha-methyl-AP4) (MAP4). However, the DCG-IV-induced depression could be reversed by the NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (AP5; 50 microM), and partially reversed by the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 5 microM). These results strongly suggest that DCG-IV is an agonist at NMDA receptors and provide further evidence against a role for metabotropic glutamate receptor group II in synaptic transmission in area CA1 of rat hippocampus.
Breakwell
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Department of Physiology, Trinity College Dublin, Ireland.
Huang
L
L
Rowan
M J
MJ
Anwyl
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003521:Cyclopropanes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D003521:Cyclopropanes; D058915:Purinergic P1 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014970:Xanthines; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D015763:2-Amino-5-phosphonovalerate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D005998:Glycine