Differential Modulation of Glutamatergic Transmission by 3,5-Dibromo-l-phenylalanine

@article{Yarotskyy2005DifferentialMO,
  title={Differential Modulation of Glutamatergic Transmission by 3,5-Dibromo-l-phenylalanine},
  author={Viktor Yarotskyy and Alexander V. Glushakov and Colin Sumners and Nikolaus Gravenstein and Donn M. Dennis and Christoph N. Seubert and Anatoly E. Martynyuk},
  journal={Molecular Pharmacology},
  year={2005},
  volume={67},
  pages={1648 - 1654}
}
An increasing body of evidence supports the hypothesis that diminished function of N-methyl-d-aspartate (NMDA) receptors and the associated increase in glutamate release and overstimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors are critical elements of the pathophysiology of schizophrenia. Here, we describe a halogenated derivative of the aromatic amino acid l-phenylalanine that 1) activates NMDA receptors, 2) depresses presynaptic glutamate release… 

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References

SHOWING 1-10 OF 31 REFERENCES
Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria
TLDR
The finding that L-Phe inhibits specifically N MDAR current in hippocampal neurons by competing for the glycine-binding site suggests a role for impaired NMDAR function in the development of mental retardation during phenylketonuria and accordingly an important role for NMD ARs in memory formation and learning.
Neuroprotective Action of Halogenated Derivatives of L-Phenylalanine
TLDR
DBrT, an endogenous halogenated derivative of L-Phe, shows promise as a representative of a novel class of neuroprotective agents by exerting significant neuroprotection in both in vitro and in vivo models of brain ischemia.
Activation of Glutamate Neurotransmission in the Prefrontal Cortex Sustains the Motoric and Dopaminergic Effects of Phencyclidine
TLDR
The findings suggest that the PFC may be a principal site for the regulation of PCP-induced stereotypy and hyperlocomotion, and that this regulation is independent of accumbal dopamine activity.
L‐phenylalanine selectively depresses currents at glutamatergic excitatory synapses
TLDR
The finding that GluR activity is significantly depressed at conditions characteristic of classical PKU indicates a potentially important contribution of impaired GLUR function to PKU‐related mental retardation and provides important insights into the potential physiological consequences of impairedGluR function.
NMDA antagonist neurotoxicity: mechanism and prevention.
TLDR
It is shown that the morphological damage can be prevented by certain anticholinergic drugs or by diazepam and barbiturates, which act at the gamma-aminobutyric acid (GABA) receptor-channel complex and are known to suppress the psychotomimetic symptoms caused by ketamine, thereby enhancing their utility as neuroprotective drugs.
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
TLDR
The findings suggest that ketamine may disrupt dopaminergic neurotransmission in the PFC as well as cognitive functions associated with this region, in part, by increasing the release of glutamate, thereby stimulating postsynaptic non-NMDA glutamate receptors.
Regulation of Neurotransmitter Release by Metabotropic Glutamate Receptors
TLDR
The neurochemical evidence for mGlu receptor‐mediated regulation of neurotransmitters, such as excitatory and inhibitory amino acids, monoamines, and neuropeptides is addressed.
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