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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.
|Item Type:||Journal Article, refereed|
|Communities & Collections:||04 Faculty of Medicine > Brain Research Institute|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||11 Feb 2008 13:13|
|Last Modified:||23 Nov 2012 14:39|
|Publisher:||Nature Publishing Group|
|WoS Citation Count:||106|
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