Abstract
The ability of activation of group I metabotropic glutamate receptors (mGluR) to induce long-term depression (LTD) was investigated in the medial perforant path of the dentate gyrus in vitro. Application of the group I agonists (RS)-3,5-dihydroxyphenylglycine (DHPG) and (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), and also the partial agonist (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF 596), induced LTD of the field EPSP. The induction of LTD is likely to be mediated via mGluR5 since CHPG and UPF 596 are selective agonists/partial agonists at that receptor. Further evidence for the involvement of group I mGluR in LTD induction was the finding, that the DHPG and low frequency stimulation induced LTD were inhibited by the group I mGluR antagonist [CRS]-1-aminoindan-1,5-dicarboxylic acid (AIDA). Investigation of the intracellular mechanisms underlying the induction of the group I mGluR-mediated LTD showed an inhibition of the LTD by the protein kinase C (PKC) inhibitor bisindolylmaleimide I and the protein tyrosine kinase inhibitor lavendustin A, but not the PKA inhibitor H89. These studies demonstrate that DHPG-induced LTD can be induced by the activation of mGluR5 followed by intracellular stimulation of PKC and tyrosine kinase.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dentate Gyrus / drug effects
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Dentate Gyrus / physiology*
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agonists / pharmacology*
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Excitatory Amino Acid Antagonists / pharmacology
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Glycine / analogs & derivatives*
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Glycine / pharmacology
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In Vitro Techniques
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Indans / pharmacology
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Indoles / pharmacology
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Isoquinolines / pharmacology
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Maleimides / 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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Phenols / pharmacology
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Phenylacetates / pharmacology*
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Protein Kinase C / metabolism
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Protein-Tyrosine Kinases / metabolism
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Rats
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Receptors, Metabotropic Glutamate / agonists
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / physiology*
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Sulfonamides*
Substances
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1-aminoindan-1,5-dicarboxylic acid
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2-chloro-5-hydroxyphenylglycine
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Excitatory Amino Acid Antagonists
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Indans
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Indoles
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Isoquinolines
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Maleimides
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Phenols
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Phenylacetates
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Receptors, Metabotropic Glutamate
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Sulfonamides
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lavendustin A
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Methoxyhydroxyphenylglycol
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Protein-Tyrosine Kinases
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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bisindolylmaleimide I
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
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Glycine
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3,4-dihydroxyphenylglycol