Article date: June 2005
By: Xiang‐Qun Gong, Anne Frandsen, Wei‐Yang Lu, Yudi Wan, Rebecca L Zabek, Darryl S Pickering, Donglin Bai in Volume 145, Issue 4, pages 449-459
The amino acid, D‐aspartate, exists in the mammalian brain and is an agonist at the N‐methyl‐D‐aspartate (NMDA) subtype of ionotropic glutamate receptors. Here, for the first time, we studied the actions of D‐aspartate on α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazolepropionate receptors (AMPARs) in acutely isolated rat hippocampal neurons.
In the presence of the NMDA receptor channel blocker, MK801, D‐aspartate inhibited kainate‐induced AMPAR current in hippocampal neurons. The inhibitory action of D‐aspartate on kainate‐induced AMPAR current was concentration‐dependent and was voltage‐independent in the tested voltage range (−80 to +60 mV).
The estimated EC50 of the L‐glutamate‐induced AMPAR current was increased in the presence of D‐aspartate, while the estimated maximum L‐glutamate‐induced AMPAR current was not changed. D‐aspartate concentration‐dependently shifted the dose–response curve of kainate to the right. Schild plot analysis indicated that D‐aspartate acts competitively to block AMPARs. The Kb for D‐aspartate was estimated to be 0.93 mM.
D‐Aspartate also blocked L‐glutamate‐induced current in Xenopus laevis oocytes that expressed recombinant homomeric AMPARs.
NMDA possessed similar inhibitory action on AMPARs. However, L‐aspartate had little inhibitory action on AMPARs.
D‐Aspartate, but not L‐aspartate, was found to reduce the amplitude of miniature excitatory postsynaptic current in cultured hippocampal neurons.
Our data are consistent with a model in which D‐aspartate directly competes with kainate and L‐glutamate in binding to the agonist binding site of AMPARs. The prevalence of D‐aspartate in the brain suggests a possible role of D‐aspartate in modulating AMPAR‐mediated fast excitatory synaptic transmission.
The amino acid, D‐aspartate, exists in the mammalian brain and is an agonist at the N‐methyl‐D‐aspartate (NMDA) subtype of ionotropic glutamate receptors. Here, for the first time, we studied the actions of D‐aspartate on α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazolepropionate receptors (AMPARs) in acutely isolated rat hippocampal neurons.
In the presence of the NMDA receptor channel blocker, MK801, D‐aspartate inhibited kainate‐induced AMPAR current in hippocampal neurons. The inhibitory action of D‐aspartate on kainate‐induced AMPAR current was concentration‐dependent and was voltage‐independent in the tested voltage range (−80 to +60 mV).
The estimated EC50 of the L‐glutamate‐induced AMPAR current was increased in the presence of D‐aspartate, while the estimated maximum L‐glutamate‐induced AMPAR current was not changed. D‐aspartate concentration‐dependently shifted the dose–response curve of kainate to the right. Schild plot analysis indicated that D‐aspartate acts competitively to block AMPARs. The Kb for D‐aspartate was estimated to be 0.93 mM.
D‐Aspartate also blocked L‐glutamate‐induced current in Xenopus laevis oocytes that expressed recombinant homomeric AMPARs.
NMDA possessed similar inhibitory action on AMPARs. However, L‐aspartate had little inhibitory action on AMPARs.
D‐Aspartate, but not L‐aspartate, was found to reduce the amplitude of miniature excitatory postsynaptic current in cultured hippocampal neurons.
Our data are consistent with a model in which D‐aspartate directly competes with kainate and L‐glutamate in binding to the agonist binding site of AMPARs. The prevalence of D‐aspartate in the brain suggests a possible role of D‐aspartate in modulating AMPAR‐mediated fast excitatory synaptic transmission.
British Journal of Pharmacology (2005) 145, 449–459. doi:10.1038/sj.bjp.0706199
DOI: 10.1038/sj.bjp.0706199
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