title: Activation of metabotropic glutamate receptors inhibits synapsin I phosphorylation in visceral sensory neurons.
abstract: Activation of glutamate metabotropic receptors (mGluRs) in nodose ganglia neurons has previously been shown to inhibit voltage-gated Ca++ currents and synaptic vesicle exocytosis. The present study describes the effects of mGluRs on depolarization-induced phosphorylation of the synaptic-vesicle-associated protein synapsin I. Depolarization of cultured nodose ganglia neurons with 60 mM KCl resulted in an increase in synapsin I phosphorylation. Application of mGluR agonists 1-aminocyclopentane-1s-3r-dicarboxylic acid (t-ACPD) and L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) either in combination or independently inhibited the depolarization induced phosphorylation of synapsin I. Application of the mGluR antagonist (RS)-alpha-Methyl-4-carboxyphenylglycine (MCPG) blocked t-ACPD-induced inhibition of synapsin phosphorylation but not the effects of L-AP4. In addition, application of either t-ACPD or L-AP4 in the absence of KCl induced depolarization had no effect on resting synapsin I phosphorylation. RT-PCR analysis of mGluR subtypes in these nodose ganglia neurons revealed that these cells only express group III mGluR subtypes 7 and 8. These results suggest that activation of mGluRs modulates depolarization-induced synapsin I phosphorylation via activation of mGluR7 and/or mGluR8 and that this process may be involved in mGluR inhibition of synaptic vesicle exocytosis in visceral sensory neurons of the nodose ganglia.
authors.affiliation: Dalton Cardiovascular Research Center, Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, MO 65255, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hay
authors.forename: C J
authors.initials: CJ
authors.lastname: Hoang
authors.forename: E M
authors.initials: EM
authors.lastname: Hasser
authors.forename: E M
authors.initials: EM
authors.lastname: Price
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008564:Membrane Potentials; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000166:cytology; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016704:Synapsins / Q000378:metabolism*
chemical_list: D000613:Aminobutyrates; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; D016704:Synapsins; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D011189:Potassium Chloride; C012729:2-amino-4-phosphonobutyric acid