Metabotropic glutamate receptors potentiate ionotropic glutamate responses in the rat dorsal horn.

The effects of the metabotropic glutamate receptor agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] were examined on responses mediated by the ionotropic glutamate receptor agonists N-methyl D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), and kainic acid (KA), in neurons acutely isolated from the dorsal horn of the rat spinal cord. (1S,3R)-ACPD produced an increase in the intracellular Ca2+ concentration in 50% of acutely isolated dorsal horn neurons, which could be prevented by blockers of voltage-sensitive Ca2+ channels. (1S,3R)-ACPD markedly potentiated increases in the intracellular Ca2+ concentration induced by NMDA, AMPA, and KA but not by 10-50 mM KCl. This potentiation occurred in all cells, required the simultaneous presence of both agonists, and was rapidly reversible. In the spinal cord slice preparation, (1S,3R)-ACPD potentiated the inward currents evoked by pressure application of AMPA, NMDA, and KA, an effect that was also rapidly reversible. These short term effects of (1S,3R)-ACPD may play an important role in the regulation of ionotropic responses mediated by glutamate in the spinal cord.