Abstract
Previously, we have found that activation of mGlu receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-DHPG, can induce long-term depression (LTD) in the CA1 region of the hippocampus and that, once established, this synaptic depression can be reversed by application of the mGlu receptor antagonist, (S)-MCPG [Palmer et al., 1997. Neuropharmacology 36, 1517-1532]. We have started to investigate the signal transduction mechanisms involved in these effects. Group I mGlu receptors couple to phospholipase C and therefore can activate protein kinase C and mobilise Ca2+ from intracellular stores. However, neither protein kinase C inhibitors (chelerythrine or Ro 31-8220) nor agents which deplete intracellular Ca2+ stores (thapsigargin or cyclopiazonic acid) were able to prevent DHPG-induced LTD. Furthermore, the ability of MCPG to reverse DHPG-induced LTD was not prevented by these compounds. These results suggest that it is unlikely that DHPG-induced LTD, or its reversal by MCPG, is produced via activation of either protein kinase C or by release of Ca2+ from intracellular stores.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids
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Animals
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Benzoates / pharmacology
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Benzophenanthridines
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Calcium / metabolism
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists / pharmacology*
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Female
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Glycine / analogs & derivatives
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Glycine / pharmacology
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Hippocampus / drug effects
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Hippocampus / physiology*
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In Vitro Techniques
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Indoles / pharmacology
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Magnesium / pharmacology
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Methoxyhydroxyphenylglycol / analogs & derivatives*
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Methoxyhydroxyphenylglycol / pharmacology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Phenanthridines / pharmacology
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Protein Kinase C / metabolism
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Rats
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Rats, Wistar
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / physiology*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Synaptic Transmission / drug effects
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Type C Phospholipases / metabolism
Substances
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Alkaloids
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Benzoates
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Benzophenanthridines
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Indoles
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Phenanthridines
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Receptors, Metabotropic Glutamate
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alpha-methyl-4-carboxyphenylglycine
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Methoxyhydroxyphenylglycol
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chelerythrine
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Protein Kinase C
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Type C Phospholipases
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Magnesium
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Calcium
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Glycine
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3,4-dihydroxyphenylglycol
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Ro 31-8220