| GCP II (NAALADase) inhibition suppresses mossy fiber-CA3 synaptic neurotransmission by a presynaptic mechanism. | |
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MedLine Citation:
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PMID: 12917384 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested the hypothesis that endogenous N-acetylaspartylglutamate (NAAG) presynaptically inhibits glutamate release at mossy fiber-CA3 synapses. For this purpose, we made use of 2-(3-mercaptopropyl)pentanedioic acid (2-MPPA), an inhibitor of glutamate carboxypeptidase II [GCP II; also known as N-acetylated alpha-linked acidic dipeptidase (NAALADase)], the enzyme that hydrolyzes NAAG into N-acetylaspartate and glutamate. Application of 2-MPPA (1-20 microM) had no effect on intrinsic membrane properties of CA3 pyramidal neurons recorded in vitro in whole cell current- or voltage-clamp mode. Bath application of 10 microM 2-MPPA suppressed evoked excitatory postsynaptic current (EPSC) amplitudes. Attenuation of EPSC amplitudes was accompanied by a significant increase in paired-pulse facilitation (50-ms interpulse intervals), suggesting that a presynaptic mechanism is involved. The group II metabotropic glutamate receptor (mGluR) antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-y l) propanoic acid (LY341495) prevented the 2-MPPA-dependent suppression of EPSC amplitudes. 2-MPPA reduced the frequencies of TTX-insensitive miniature EPSCs (mEPSC), without affecting their amplitudes, further supporting a presynaptic action for GCP II inhibition. 2-MPPA-induced reduction of mEPSC frequencies was prevented by LY341495, reinforcing the role of presynaptic group II mGluR. Because GCP II inhibition is thought to increase NAAG levels, these results suggest that NAAG suppresses synaptic transmission at mossy fiber-CA3 synapses through presynaptic activation of group II mGluRs. |
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Authors:
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Emilio R Garrido Sanabria; Krystyna M Wozniak; Barbara S Slusher; Asaf Keller |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-08-13 |
Journal Detail:
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Title: Journal of neurophysiology Volume: 91 ISSN: 0022-3077 ISO Abbreviation: J. Neurophysiol. Publication Date: 2004 Jan |
Date Detail:
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Created Date: 2004-01-12 Completed Date: 2004-03-01 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0375404 Medline TA: J Neurophysiol Country: United States |
Other Details:
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Languages: eng Pagination: 182-93 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore 21201, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids
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pharmacology Analysis of Variance Animals Animals, Newborn Calcium / pharmacology Chemokine CXCL6 Chemokines, CXC / antagonists & inhibitors* Dose-Response Relationship, Drug Drug Interactions Electric Conductivity Electric Stimulation Enzyme Inhibitors / pharmacology Excitatory Amino Acid Antagonists / pharmacology Excitatory Postsynaptic Potentials / drug effects, physiology Glutarates / pharmacology* Male Mossy Fibers, Hippocampal / drug effects*, physiology Neural Inhibition / drug effects* Neurons / drug effects, physiology Patch-Clamp Techniques Presynaptic Terminals / drug effects*, physiology Probability Rats Sulfhydryl Compounds / pharmacology* Synaptic Transmission / drug effects*, physiology Time Factors Xanthenes / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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NS-31078/NS/NINDS NIH HHS; NS-35360/NS/NINDS NIH HHS; R01 NS031078-12/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(3-mercaptopropyl)pentanedioic acid; 0/Amino Acids; 0/Chemokine CXCL6; 0/Chemokines, CXC; 0/Enzyme Inhibitors; 0/Excitatory Amino Acid Antagonists; 0/Glutarates; 0/LY 341495; 0/Sulfhydryl Compounds; 0/Xanthenes; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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