NMDA receptors are Ca2+-permeable ion channels. The activation of NMDA receptors requires agonist glutamate and co-agonist glycine. Recent evidence indicates that NMDA receptor also has metabotropic function. Here we report that in cultured mouse hippocampal neurons, glycine increases AMPA receptor-mediated currents independent of the channel activity of NMDA receptors and the activation of gly...

Ca(2+)-permeable AMPA receptors are densely expressed in the spinal dorsal horn, but their functional significance in pain processing is not understood. By disrupting the genes encoding GluR-A or GluR-B, we generated mice exhibiting increased or decreased numbers of Ca(2+)-permeable AMPA receptors, respectively. Here, we demonstrate that AMPA receptors are critical determinants of nociceptive p...

Naturally occurring glutamate analogs, such as kainate and domoate, which cause excitotoxic shellfish poisoning, induce nondesensitizing responses at neuronal alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. In addition to acting on AMPA receptors, kainate and domoate also activate high-affinity kainate-type glutamate receptors. The receptor type that mediates their ne...

Postsynaptic differentiation during glutamatergic synapse formation is poorly understood. Using a novel biophysical approach, we have investigated the distribution and density of functional glutamate receptors and characterized their clustering during synaptogenesis in cultured hippocampal neurons. We found that functional alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) and N-methyl-...

We have explored the ability of axons from spinal and hippocampal neurons to aggregate NMDA- and AMPA-type glutamate receptors on each other as a way of exploring the molecular differences between their presynaptic elements. Spinal axons, which normally cluster only AMPA-type glutamate receptors on other spinal neurons, cluster both AMPA- and NMDA-type glutamate receptors on the dendritic shaft...

The effects of cyclothiazide, a drug which blocks AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor desensitization, were tested on binding of [3H]AMPA to rat brain membranes. Cyclothiazide reduced [3H]AMPA binding by lowering the apparent affinity of the AMPA receptor. The magnitude of the decrease was temperature dependent and greater for membrane-bound than for solubil...

In the brain, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate glutamatergic neurotransmission and, when intensely activated, can induce excitotoxic cell death. In addition to their ionotropic properties, however, AMPA receptors have been functionally coupled to a variety of signal transduction events involving Src-family kinases, G-proteins, and the mitogen-activat...

Ionotropic glutamate receptors from the AMPA and kainate subfamilies share many functional and structural features, but it is unclear whether this similarity extends to the molecular mechanisms underlying receptor desensitization. The current model for desensitization in AMPA receptors involves the rearrangement of dimers formed between subunit agonist binding domains. Key evidence for this has...

in vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area (vta) in freely moving rats. intraperitoneal (i.p.) injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. only a minor tolerance developed to this dosage of morphine. ap-s (2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.), a nmda r...