1381041

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

Article date: 1992/8/1

PubMed ID: 1381041

Journal name: Molecular pharmacology (ISSN: 0026-895X)

ABSTRACT

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.

Author List: Bleakman D, Rusin K I, Chard P S, Glaum S R, Miller R J

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Glutamates; Receptors, Glutamate; Receptors, Neurotransmitter; Cycloleucine; 1-amino-1,3-dicarboxycyclopentane; Ibotenic Acid; Glutamic Acid; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Kainic Acid; Calcium;

Mesh terms: Animals; Calcium/metabolism; Cycloleucine/analogs & derivatives; Drug Synergism; Glutamates/pharmacology; Glutamic Acid; Ibotenic Acid/analogs & derivatives; Ion Channel Gating/physiology; Kainic Acid/pharmacology; Myocardial Contraction/drug effects; N-Methylaspartate/pharmacology; Neurons/drug effects; Rats; Receptors, Glutamate; Receptors, Neurotransmitter/drug effects; Spinal Cord/drug effects; Synapses/drug effects; Synaptic Transmission/drug effects; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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