An investigation into signal transduction mechanisms involved in DHPG-induced LTD in the CA1 region of the hippocampus

Neuropharmacology. 1999 Oct;38(10):1585-96. doi: 10.1016/s0028-3908(99)00062-3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids
  • Animals
  • Benzoates / pharmacology
  • Benzophenanthridines
  • Calcium / metabolism
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Indoles / pharmacology
  • Magnesium / pharmacology
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Phenanthridines / pharmacology
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Synaptic Transmission / drug effects
  • Type C Phospholipases / metabolism

Substances

  • Alkaloids
  • Benzoates
  • Benzophenanthridines
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Indoles
  • Phenanthridines
  • Receptors, Metabotropic Glutamate
  • alpha-methyl-4-carboxyphenylglycine
  • Methoxyhydroxyphenylglycol
  • chelerythrine
  • Protein Kinase C
  • Type C Phospholipases
  • Magnesium
  • Calcium
  • Glycine
  • 3,4-dihydroxyphenylglycol
  • Ro 31-8220