HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 91/1/182    most recent 00465.2003v2 00465.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Garrido Sanabria, E. R. Articles by Keller, A. Search for Related Content PubMed PubMed Citation Articles by Garrido Sanabria, E. R. Articles by Keller, A.

GCP II (NAALADase) Inhibition Suppresses Mossy Fiber-CA3 Synaptic Neurotransmission by a Presynaptic Mechanism

¹ Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore 21201; ² Guilford Pharmaceuticals, Baltimore, Maryland 21224

Submitted 3 May 2003; accepted in final form 6 August 2003

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 µM) 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 µM 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.

This article has been cited by other articles:

				B. Poschel, B. Wroblewska, U. Heinemann, and D. Manahan-Vaughan The Metabotropic Glutamate Receptor mGluR3 is Critically Required for Hippocampal Long-term Depression and Modulates Long-term Potentiation in the Dentate Gyrus of Freely Moving Rats Cereb Cortex, September 1, 2005; 15(9): 1414 - 1423. [Abstract] [Full Text] [PDF]