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Neuropharmacology. 2015 Oct;97:95-103. doi: 10.1016/j.neuropharm.2015.05.011. Epub 2015 May 19.

Effects of 3-aminoglutarate, a "silent" false transmitter for glutamate neurons, on synaptic transmission and epileptiform activity.

Author information

1
Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA.
2
Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612, USA.
3
Department of Biological Sciences, Allergan Inc., 2525 Dupont Drive, Irvine, CA 92612, USA. Electronic address: li_yongxin@allergan.com.
4
Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address: gongchen@psu.edu.

Abstract

Pharmacological tools that interact with the mechanisms that regulate vesicular filling and release of the neurotransmitter L-glutamate would be of enormous value. In this study, we provide physiological evidence that the glutamate analog, 3-aminoglutarate (3-AG), acts as a false transmitter to reduce presynaptic glutamate release. 3-AG inhibits glutamate-mediated neurotransmission both in primary neuronal cultures and in brain slices with more intact neural circuits. When assayed with the low affinity glutamate receptor antagonist γ-DGG, we demonstrate that 3-AG significantly reduces the synaptic cleft glutamate concentration, suggesting that 3-AG may act as a false transmitter to compete with glutamate during vesicle filling. Furthermore, using three different epileptic models (Mg(2+)-free, 4-AP, and high K(+)), we demonstrate that 3-AG is capable of suppressing epileptiform activity both before and after its induction. Our studies, along with those of the companion paper by Foster et al. (2015) indicate that 3-AG is a "silent" false transmitter for glutamate neurons that is a useful pharmacological tool to probe the mechanisms governing vesicular storage and release of glutamate under both physiological and pathophysiological conditions. 3-AG may have potential therapeutic value in conditions where the glutamate neurotransmitter system is pathologically overactive.

KEYWORDS:

Epilepsy; False transmitter; Glutamate; Synaptic transmission; Synaptic vesicle; Transmitter release

[Indexed for MEDLINE]

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