L-TRANs-Pyrrolidine-2,4-dicarboxylate and cis-1-aminocyclobutane-1, 3-dicarboxylate behave as transportable, competitive inhibitors of the high-affinity glutamate transporters

Griffiths, Roger; Dunlop, John; Gorman, Adrienne M.; Senior, Jeanette; Grieve, Angus

doi:10.1016/0006-2952(94)90016-7

Cited by 82 publications

(56 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the presence of t-PDC, LTD was induced by LFS. However, t-PDC has been reported to not only block uptake but to reverse glutamate transport (Griffiths et al, 1994;Volterra et al, 1996) and increase ambient glutamate levels. However, in our studies, the application of t-PDC had no effect on synaptic transmission in the absence of LFS.…”

Section: Extrasynaptic Nmdars Mediate Ltd In Adult Cortexmentioning

confidence: 99%

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Massey¹,

Johnson²,

Moult³

et al. 2004

J. Neurosci.

616

577

View full text Add to dashboard Cite

It is widely believed that long-term depression (LTD) and its counterpart, long-term potentiation (LTP), involve mechanisms that are crucial for learning and memory. However, LTD is difficult to induce in adult cortex for reasons that are not known. Here we show that LTD can be readily induced in adult cortex by the activation of NMDA receptors (NMDARs), after inhibition of glutamate uptake. Interestingly there is no need to activate synaptic NMDARs to induce this LTD, suggesting that LTD is triggered primarily by extrasynaptic NMDA receptors. We also find that de novo LTD requires the activation of NR2B-containing NMDAR, whereas LTP requires activation of NR2A-containing NMDARs. Surprisingly another form of LTD, depotentiation, requires activation of NR2A-containing NMDARs. Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex.

show abstract

Section: Extrasynaptic Nmdars Mediate Ltd In Adult Cortexmentioning

confidence: 99%

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Massey¹,

Johnson²,

Moult³

et al. 2004

J. Neurosci.

616

577

View full text Add to dashboard Cite

show abstract

“…served were not due simply due to accumulation of synaptic glutamate via heteroexchange of glutamate. Rebillard and colleagues (2003) observed dose-dependent reductions in CAP amplitudes when perfusing the scala tympani with relatively high concentrations of PDC, a broad-spectrum, substrate-based, glutamate transporter inhibitor (Griffiths et al 1994). Their careful pharmacological analysis demonstrated that the effects they observed were consistent with activation of AMPA receptors.…”

Section: Pharmacologymentioning

confidence: 99%

Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

Chen

Kujawa

Sewell

2010

Journal of Neurophysiology

View full text Add to dashboard Cite

Chen Z, Kujawa SG, Sewell WF. Functional roles of highaffinity glutamate transporters in cochlear afferent synaptic transmission in the mouse. J Neurophysiol 103: 2581-2586, 2010. First published March 10, 2010 doi:10.1152/jn.00018.2010. In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. L-serine-O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 M for 220 min), TBOA (200 M for 220 min), or SOS (100 M for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noiseinduced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate-or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation.

show abstract

“…It has been proposed that the uptake of the transportable inhibitor PDC by GLU transporters induces release of intracellular GLU by heteroexchange (Griffiths et al 1994), based on the following evidence. In superfused cultured cerebellar granule cells and astrocytes (Griffiths et al 1994;Waagepetersen et al 2001) and in synaptosomes (Koch et al 1999), the addition of PDC induces release of D-[ 3 H]aspartate (a nonmetabolizable analog of GLU) preloaded into the cell. In reconstituted liposomes containing GLU transporters, preloaded 3 H-GLU is released by PDC (Volterra et al 1996).…”

Section: Contribution Of Neurotransmitter Glu Ecf To Gln Synthesismentioning

confidence: 99%

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Kanamori

Ross

Kondrat

2002

Journal of Neurochemistry

View full text Add to dashboard Cite

Glial uptake of neurotransmitter glutamate (GLU) from the extracellular fluid was studied in vivo in rat brain by 13 C NMR and microdialysis combined with gas-chromatography/massspectrometry. Brain GLU C5 was 13 C enriched by intravenous [2,5-13 C]glucose infusion, followed by [ 12 C]glucose infusion to chase 13 C from the small glial GLU pool. This leaves [5-13 C]GLU mainly in the large neuronal metabolic pool and the vesicular neurotransmitter pool. During the chase, the 13 C enrichment of whole-brain GLU C5 was significantly lower than that of extracellular GLU (GLU ECF ) derived from exocytosis of vesicular GLU. Glial uptake of neurotransmitter N enrichment of precursor NH 3 (0.87 ± 0.014), the rate of synthesis of GLN (V¢ GLN ), derived from neurotransmitter GLU ECF , was determined to be 6.4 ± 0.44 lmol/g/h. Comparison with V GLN measured previously by an independent method showed that the neurotransmitter provides 80-90% of the substrate GLU pool for GLN synthesis. Hence, under our experimental conditions, the rate of 6.4 ± 0.44 lmol/g/h also represents a reasonable estimate for the rate of glial uptake of GLU ECF , a process that is crucial for protecting the brain from GLU excitotoxicity.

show abstract

L-TRANs-Pyrrolidine-2,4-dicarboxylate and cis-1-aminocyclobutane-1, 3-dicarboxylate behave as transportable, competitive inhibitors of the high-affinity glutamate transporters

Cited by 82 publications

References 38 publications

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR

Contact Info

Product

Resources

About

L-TRANs-Pyrrolidine-2,4-dicarboxylate and cis-1-aminocyclobutane-1, 3-dicarboxylate behave as transportable, competitive inhibitors of the high-affinity glutamate transporters

Cited by 82 publications

References 38 publications

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression

Functional Roles of High-Affinity Glutamate Transporters in Cochlear Afferent Synaptic Transmission in the Mouse

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and13C NMR

Contact Info

Product

Resources

About

Glial uptake of neurotransmitter glutamate from the extracellular fluid studiedin vivoby microdialysis and¹³C NMR