Abstract
Synaptically released glutamate activates ionotropic and metabotropic receptors at central synapses. Metabotropic glutamate receptors (mGluRs) are thought to modulate membrane conductances through transduction cascades involving G proteins. Here we show, in CA3 pyramidal cells from rat hippocampus, that synaptic activation of type 1 mGluRs by mossy fiber stimulation evokes an excitatory postsynaptic response independent of G-protein function, while inhibiting an afterhyperpolarization current through a G-protein-coupled mechanism. Experiments using peptide activators and specific inhibitors identified a Src-family protein tyrosine kinase as a component of the G-protein-independent transduction pathway. These results represent the first functional evidence for a dual signaling mechanism associated with a heptahelical receptor such as mGluR1, in which intracellular transduction involves activation of either G proteins or tyrosine kinases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / antagonists & inhibitors
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ATP-Binding Cassette Transporters / metabolism
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Adenosine / pharmacology
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Amino Acid Sequence
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Amino Acid Transport System X-AG
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Animals
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Cations / metabolism
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Electric Conductivity
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Electric Stimulation
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Enzyme Activation
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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GABA-B Receptor Antagonists
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Heterotrimeric GTP-Binding Proteins / agonists
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Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors
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Heterotrimeric GTP-Binding Proteins / physiology*
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Mossy Fibers, Hippocampal / drug effects
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Mossy Fibers, Hippocampal / physiology
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Organ Culture Techniques
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Potassium / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases / antagonists & inhibitors
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Protein Tyrosine Phosphatases / metabolism
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Pyramidal Cells / drug effects
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Pyramidal Cells / physiology*
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Rats
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Rats, Wistar
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Receptors, GABA-B / physiology
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism*
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Signal Transduction* / drug effects
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src-Family Kinases / antagonists & inhibitors
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src-Family Kinases / metabolism*
Substances
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ATP-Binding Cassette Transporters
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Amino Acid Transport System X-AG
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Cations
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Excitatory Amino Acid Antagonists
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GABA-B Receptor Antagonists
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Receptors, GABA-B
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Receptors, Metabotropic Glutamate
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metabotropic glutamate receptor type 1
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src-Family Kinases
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatases
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Heterotrimeric GTP-Binding Proteins
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Adenosine
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Potassium