ArticleJournal of neurophysiology2004
GCP II (NAALADase) inhibition suppresses mossy fiber-CA3 synaptic neurotransmission by a presynaptic mechanism.
Article in Journal of neurophysiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 74 citations in OpenAlex.
- Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Divergent changes in PBN excitability in a mouse model of neuropathic pain.bioRxiv : the preprint server for biology · 2023Article
- GRM2 Regulates Functional Integration of Adult-Born DGCs by Paradoxically Modulating MEK/ERK1/2 Pathway.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Neurexin-2 restricts synapse numbers and restrains the presynaptic release probability by an alternative splicing-dependent mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Troriluzole inhibits methamphetamine place preference in rats and normalizes methamphetamine-evoked glutamate carboxypeptidase II (GCPII) protein levels in the mesolimbic pathway.Drug and alcohol dependence · 2023Article
- Glutamate Metabotropic Receptor Type 3 (mGlu3) Localization in the Rat Prelimbic Medial Prefrontal Cortex.Frontiers in neuroanatomy · 2022Article
- The Brain Metabolic Signature in Superagers Using In VivoAJNR. American journal of neuroradiology · 2021Article
- An Amygdalo-Parabrachial Pathway Regulates Pain Perception and Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Dendritic Localization and Exocytosis of NAAG in the Rat Hippocampus.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.Neurochemical research · 2017Article
- Anisotropically organized three-dimensional culture platform for reconstruction of a hippocampal neural network.Nature communications · 2017Article
- A role for the locus coeruleus in the analgesic efficacy of N-acetylaspartylglutamate peptidase (GCPII) inhibitors ZJ43 and 2-PMPA.Molecular pain · 2017Article
- Long-Term Intake ofEvidence-based complementary and alternative medicine : eCAM · 2017Article
- The therapeutic and diagnostic potential of the prostate specific membrane antigen/glutamate carboxypeptidase II (PSMA/GCPII) in cancer and neurological disease.British journal of pharmacology · 2016Review
- Glutamate carboxypeptidase II gene knockout attenuates oxidative stress and cortical apoptosis after traumatic brain injury.BMC neuroscience · 2016Article
- High-field proton magnetic resonance spectroscopy reveals metabolic effects of normal brain aging.Neurobiology of aging · 2014Article
- NAAG peptidase inhibitor improves motor function and reduces cognitive dysfunction in a model of TBI with secondary hypoxia.Brain research · 2013Article
- NAAG peptidase inhibition in the periaqueductal gray and rostral ventromedial medulla reduces flinching in the formalin model of inflammation.Molecular pain · 2012Article
- NAAG peptidase inhibitor reduces cellular damage in a model of TBI with secondary hypoxia.Brain research · 2012Article
- Effects of N-acetylaspartylglutamate (NAAG) peptidase inhibition on release of glutamate and dopamine in prefrontal cortex and nucleus accumbens in phencyclidine model of schizophrenia.The Journal of biological chemistry · 2012Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
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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Registered trials
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