|GCP II (NAALADase) inhibition suppresses mossy fiber-CA3 synaptic neurotransmission by a presynaptic mechanism.|
|PMID: 12917384 Owner: NLM Status: MEDLINE|
|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.|
|Emilio R Garrido Sanabria; Krystyna M Wozniak; Barbara S Slusher; Asaf Keller|
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|Type: Comparative Study; In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. Date: 2003-08-13|
|Title: Journal of neurophysiology Volume: 91 ISSN: 0022-3077 ISO Abbreviation: J. Neurophysiol. Publication Date: 2004 Jan|
|Created Date: 2004-01-12 Completed Date: 2004-03-01 Revised Date: 2014-09-20|
Medline Journal Info:
|Nlm Unique ID: 0375404 Medline TA: J Neurophysiol Country: United States|
|Languages: eng Pagination: 182-93 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Analysis of Variance
Calcium / pharmacology
Chemokines, CXC / antagonists & inhibitors*
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
Excitatory Postsynaptic Potentials / drug effects, physiology
Glutarates / pharmacology*
Mossy Fibers, Hippocampal / drug effects*, physiology
Neural Inhibition / drug effects*
Neurons / drug effects, physiology
Presynaptic Terminals / drug effects*, physiology
Sulfhydryl Compounds / pharmacology*
Synaptic Transmission / drug effects*, physiology
Xanthenes / pharmacology
|NS-31078/NS/NINDS NIH HHS; NS-35360/NS/NINDS NIH HHS; R01 NS031078/NS/NINDS NIH HHS; R01 NS031078-12/NS/NINDS NIH HHS|
|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; SY7Q814VUP/Calcium|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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