title: G-protein-independent signaling mediated by metabotropic glutamate receptors.
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.
authors.affiliation: Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Heuss
authors.forename: M
authors.initials: M
authors.lastname: Scanziani
authors.forename: B H
authors.initials: BH
authors.lastname: Gähwiler
authors.forename: U
authors.initials: U
authors.lastname: Gerber
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000494:pharmacology; D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002412:Cations / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation; D004789:Enzyme Activation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D058788:GABA-B Receptor Antagonists; D020962:Heterotrimeric GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011188:Potassium / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002412:Cations; D018691:Excitatory Amino Acid Antagonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D019061:src-Family Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D020962:Heterotrimeric GTP-Binding Proteins; D000241:Adenosine; D011188:Potassium