The GluR2 (GluR-B) hypothesis: Ca2+-permeable AMPA receptors in neurological disorders

Pellegrini‐Giampietro, Domenico E.; Gorter, Jan A.; Bennett, Michael V. L.; Zukin, R. Suzanne

doi:10.1016/s0166-2236(97)01100-4

Cited by 506 publications

(320 citation statements)

References 69 publications

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“…These adaptations are mediated by Ca 2 + influx through the channel pore. Ca 2 + can pass through NMDA receptors (Connor et al, 1988;MacDermott et al, 1986), kainate receptors (Egebjerg & Heinemann, 1993;Kohler et al, 1993), and, under some circumstances, AMPA receptors (Hume et al, 1991;Nakanishi, 1992;Pellegrini-Giampietro et al, 1997). The Ca 2 + permeability of AMPA receptors is determined by the GluR2 subunit.…”

Section: Pharmacology Of Glutamate Receptorsmentioning

confidence: 99%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

292

165

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The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.

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Section: Pharmacology Of Glutamate Receptorsmentioning

confidence: 99%

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Konradi

Heckers

2003

Pharmacology & Therapeutics

292

165

View full text Add to dashboard Cite

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“…Relative reductions of GluR2 receptors may increase susceptibility to excitotoxic damage. 14 An alternate possibility is that an increased concentration of GluR1 receptors in the flip isoform, with their enhanced Molecular Psychiatry resistance to desensitization following chronic glutamate exposure, might underlie the enhanced vulnerability of certain neurons to excitotoxic death. During normal AMPA receptor ontogeny in regions such as hippocampus and cerebellum, a developmental switch from the alternatively spliced flip to the flop isoform, corresponding to a declining need for neuronal pruning, occurs at the same timepoint at which GluR1 receptors are increased in NBD animals.…”

Section: S35mentioning

confidence: 99%

Infectious and immune factors in neurodevelopmental damage

Hornig

Mervis²,

Hoffman

et al. 2002

Mol Psychiatry

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“…AMPA receptors exist in Ca2-permeable and -impermeable forms, depending on the presence of G!uR2 subunits. These subunits have been shown to be down-regulated in vuh~erable neurones in animal models of forebrain ischaemia and in epilepsy (see Pellegrini-Giampietro et a!., 1997).…”

mentioning

confidence: 99%

Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain

Mutel

Trube

Klingelschmidt

et al. 1998

Journal of Neurochemistry

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The distribution and abundance of specific binding sites (=95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2> binding in layers 3-6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 nM, the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (=2.6 and 0.4 pmol/mg of protein, respectively). Ro 48-8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported. Key Words: a-Amino-3-hydroxy-5-methylisoxazole-4-propionate-9-lmidazol-1 -yl-8-nitro-2,3, 5,6-tetrahydro- High-affinity a-aniino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors are ligand-gated cation channels for L-glutalnate, the major excitatory transmitter in the mammalian CNS. Their activation mediates fast transmission at glutamatergic synapses. The receptors, heterooligomeric proteins composed of the subunits G1uR1 -4 with flip and flop forms (Hollmann and Heinemann, 1994;Bettler and Mulle, 1995;Barnard, 1997), play key roles in CNS physiology and pathology. AMPA receptor subunits G1uR1 -4 are differentially regulated during ontogeny, and in adult rat brain they have only partially overlapping distributions (Keinanen et al

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The GluR2 (GluR-B) hypothesis: Ca2+-permeable AMPA receptors in neurological disorders

Cited by 506 publications

References 69 publications

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Infectious and immune factors in neurodevelopmental damage

Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain

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The GluR2 (GluR-B) hypothesis: Ca2+-permeable AMPA receptors in neurological disorders

Cited by 506 publications

References 69 publications

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment

Infectious and immune factors in neurodevelopmental damage

Binding Characteristics of a Potent AMPA Receptor Antagonist [3H]Ro 48‐8587 in Rat Brain

Contact Info

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Binding Characteristics of a Potent AMPA Receptor Antagonist [³H]Ro 48‐8587 in Rat Brain