Document Detail


Immunohistological and electrophysiological evidence that N-acetylaspartylglutamate is a co-transmitter at the vertebrate neuromuscular junction.
MedLine Citation:
PMID:  23134476     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunohistochemical studies previously revealed the presence of the peptide transmitter N-acetylaspartylglutamate (NAAG) in spinal motor neurons, axons and presumptive neuromuscular junctions (NMJs). At synapses in the central nervous system, NAAG has been shown to activate the type 3 metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular peptidase, glutamate carboxypeptidase II. The present study tested the hypothesis that NAAG meets the criteria for classification as a co-transmitter at the vertebrate NMJ. Confocal microscopy confirmed the presence of NAAG immunoreactivity and extended the resolution of the peptide's location in the lizard (Anolis carolinensis) NMJ. NAAG was localised to a presynaptic region immediately adjacent to postsynaptic acetylcholine receptors. NAAG was depleted by potassium-induced depolarisation and by electrical stimulation of motor axons. The NAAG receptor, mGluR3, was localised to the presynaptic terminal consistent with NAAG's demonstrated role as a regulator of synaptic release at central synapses. In contrast, glutamate receptors, type 2 metabotropic glutamate receptor (mGluR2) and N-methyl-d-aspartate, were closely associated with acetylcholine receptors in the postsynaptic membrane. Glutamate carboxypeptidase II, the NAAG-inactivating enzyme, was identified exclusively in perisynaptic glial cells. This localisation was confirmed by the loss of immunoreactivity when these cells were selectively eliminated. Finally, electrophysiological studies showed that exogenous NAAG inhibited evoked neurotransmitter release by activating a group II metabotropic glutamate receptor (mGluR2 or mGluR3). Collectively, these data support the conclusion that NAAG is a co-transmitter at the vertebrate NMJ.
Authors:
Kathryn K Walder; Steve B Ryan; Tomasz Bzdega; Rafal T Olszewski; Joseph H Neale; Clark A Lindgren
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-08
Journal Detail:
Title:  The European journal of neuroscience     Volume:  37     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-07     Completed Date:  2013-06-11     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  118-29     Citation Subset:  IM    
Copyright Information:
© 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dipeptides / analysis,  pharmacology*
Excitatory Amino Acid Agonists / pharmacology
Glutamate Carboxypeptidase II / analysis
Immunohistochemistry
Lizards
Miniature Postsynaptic Potentials / drug effects*
Motor Neurons / chemistry,  physiology
N-Methylaspartate / pharmacology
Neuromuscular Junction / chemistry*,  physiology
Neurotransmitter Agents / pharmacology*
Potassium / pharmacology
Presynaptic Terminals / chemistry
Receptors, Cholinergic / analysis
Receptors, Metabotropic Glutamate / analysis
Grant Support
ID/Acronym/Agency:
NS038080/NS/NINDS NIH HHS; NS072735/NS/NINDS NIH HHS; R15 NS072735/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Dipeptides; 0/Excitatory Amino Acid Agonists; 0/Neurotransmitter Agents; 0/Receptors, Cholinergic; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 2; 0/metabotropic glutamate receptor 3; 3106-85-2/N-acetyl-1-aspartylglutamic acid; 6384-92-5/N-Methylaspartate; EC 3.4.17.21/Glutamate Carboxypeptidase II; RWP5GA015D/Potassium
Comments/Corrections

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