<scp>D</scp>‐Aspartate and NMDA, but not <scp>L</scp>‐aspartate, block AMPA receptors in rat hippocampal neurons

Gong, Xiang-Qun; Frandsen, Anne; Lu, Wei‐Yang; Wan, Yudi; Zabek, Rebecca L. ZabekR.L.; Pickering, Darryl S.; Bai, Donglin

doi:10.1038/sj.bjp.0706199

Cited by 38 publications

(23 citation statements)

References 39 publications

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“…Activation of AMPA receptors by its cognate agonist or Group I metabotropic glutamate receptors with DHPG failed to stimulate GLUT1. In contrast, D-aspartate, a substrate of the Na 1 -glutamate cotransporter that does not stimulate AMPA receptors or metabotropic glutamate receptors (Gong et al, 2005;Huang et al, 2005), effectively stimulated GLUT1. With D-aspartate, (71 6 5)% of the cells responded with a significant increase in hexose uptake (n 5 48 cells in six experiments), stimulation which was often stronger than that achieved with glutamate (for example compare Figs.…”

Section: -Glutamate Cotransporter Mediates the Stimulation Of Glut1mentioning

confidence: 89%

Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

Porras

Ruminot

Loaiza

et al. 2007

Glia

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Glutamate triggers an acute stimulation of the glucose transporter GLUT1 in cultured astrocytes, a phenomenon thought to facilitate energy delivery to active areas in the brain. Here we have explored the cell signaling mechanisms involved in this response. Half-stimulation of GLUT1 occurred at low micromolar glutamate, thus within the physiological range estimated in brain interstitium. The effect was mimicked by D-aspartate and inhibited by L-threo-beta-benzyloxyaspartate or Na(+) replacement with NMDG(+), showing the participation of the Na(+)-glutamate co-transporter. AMPA and the mGLURI agonist DHPG had no effect. The stimulation of GLUT1 was fully inhibited by ouabain, but independent activation of the Na(+)/K(+) ATPase pump with gramicidin did not affect glucose transport. Simultaneous with the Na(+) rise, glutamate and D-aspartate triggered a Ca(2+)signal, whose inhibition with BAPTA prevented the stimulation of GLUT1. However, an isolated Ca(2+) signal, triggered with endothelin 1, ATP or DHPG, did not affect glucose transport. The stimulation of GLUT1 could finally be mimicked by simultaneous induction of Na(+) and Ca(2+) signals. The requirement for both cations in the stimulation of the astrocytic glucose transporter, may help to explain how glucose metabolism in the brain is strongly activated by glutamate, but not by GABA or by inter-astrocytic signaling.

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Section: -Glutamate Cotransporter Mediates the Stimulation Of Glut1mentioning

confidence: 89%

Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

Porras

Ruminot

Loaiza

et al. 2007

Glia

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“…Our earlier report demonstrated that D-aspartate was able to competitively block AMPARs in hippocampal neurons (Gong et al 2005), whereas L-aspartate was virtually free of blocking action. Here we observed similar actions of Dserine and L-serine on AMPARs in the same type of neurons.…”

Section: Other D-amino Acids Also Exhibit Inhibitory Effect On Ampa Rmentioning

confidence: 99%

“…Neurons in CA1 area were isolated from hippocampal slices taken from 2-to 5-week postnatal Sprague-Dawley rats as described previously (Bai et al 2002;Gong et al 2005). Briefly, the rats were anesthetized with halothane and decapitated.…”

Section: Acute Isolation Of Hippocampal Neurons and Whole-cell Patch mentioning

confidence: 99%

d-Serine inhibits AMPA receptor-mediated current in rat hippocampal neurons

Gong

Zabek

Bai

2007

Can. J. Physiol. Pharmacol.

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D-Serine, a recently identified gliotransmitter, serves as an endogenous coagonist binding to the glycine site of N-methyl-D-aspartate (NMDA) receptors. However, it is not clear whether this native ligand is able to bind to and modulate alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. In the present study, we showed that D-serine was able to concentration-dependently inhibit kainate-induced AMPA receptor-mediated current in acutely isolated hippocampal neurons. The blocking action of D-serine on AMPA receptors was characterized by a shift in concentration-response curve of kainate-induced current to the right with no change in the maximal response and independent of holding potential in the range of -80 to +60 mV. This is consistent with a model that D-serine is a competitive antagonist on AMPA receptors. In contrast, L-serine did not exert such an inhibitory action. Consistent with this observation, we found that several D-isoforms, but not L-isoforms, of endogenous and exogenous amino acids were able to block AMPA receptors. These results indicate that there is a low affinity and stereo-selective site at the agonist binding pocket of AMPA receptors for these D-amino acids. More importantly, vesicular-released endogenous D-serine from astrocytes could potentially modulate AMPA receptors in synaptic transmission in hippocampus.

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“…␣-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Kainate, and ␦ Receptor Agonists Glutamate activates all AMPA and kainate receptors by binding within the cleft between domains D1 and D2 of the LBD to induce domain closure. Neither NMDA nor L-aspartate can activate the non-NMDA receptors, and D-aspartate acts as a low-affinity competitive antagonist for native AMPA receptors (Gong et al, 2005). In the structure of the glutamate-bound GluA2 LBD (Fig.…”

Section: Agonist and Antagonist Pharmacologymentioning

confidence: 99%

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

et al. 2010

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D‐Aspartate and NMDA, but not L‐aspartate, block AMPA receptors in rat hippocampal neurons

Cited by 38 publications

References 39 publications

Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

d-Serine inhibits AMPA receptor-mediated current in rat hippocampal neurons

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

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D‐Aspartate and NMDA, but not L‐aspartate, block AMPA receptors in rat hippocampal neurons

Cited by 38 publications

References 39 publications

Na+‐Ca2+ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

Na+‐Ca2+ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

d-Serine inhibits AMPA receptor-mediated current in rat hippocampal neurons

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

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Product

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Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes

Na⁺‐Ca²⁺ cosignaling in the stimulation of the glucose transporter GLUT1 in cultured astrocytes