Metabotropic glutamate receptor agonist DCG-IV as NMDA receptor agonist in immature rat hippocampal neurons

Abstract

The electrophysiological action of (2S,1'R;2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) on the NMDA receptor was investigated with the help of concentration-jump experiments on freshly dissociated hippocampal CA1 and CA3 neurons of rats. Inward currents elicited by a pulse of DCG-IV were insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be blocked by D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and magnesium and enhanced by glycine. The substance displayed cross-desensitization with NMDA but not with kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Dose-response curves showed that DCG-IV was weaker than NMDA but more potent than glutamate in eliciting agonist-gated currents. From these data we conclude that DCG-IV has to be used with caution as a tool for the investigation of metabotropic glutamate receptors.