An investigation into signal transduction mechanisms involved in DHPG-induced LTD in the CA1 region of the hippocampus.
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.
Schnabel
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MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, UK. r.schnabel@bristol.ac.uk
Kilpatrick
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IC
Collingridge
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GL
D000470:Alkaloids; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
D000470:Alkaloids; D001565:Benzoates; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; D010617:Phenanthridines; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D008734:Methoxyhydroxyphenylglycol; C016299:chelerythrine; D011493:Protein Kinase C; D010738:Type C Phospholipases; D008274:Magnesium; D002118:Calcium; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol; C064758:Ro 31-8220