The depolarising population response to the excitatory amino acids, quisqualate and AMPA, in slices of cerebral cortex of the rat have been compared. Their respective dose-response curves had a similar maximum but the slope of the curve for AMPA was consistently steeper than that for quisqualate. The dose-response curves for AMPA had a mean log EC50 of -5.18 +/- 0.05, which was significantly different from -4.62 +/- 0.07 the mean log EC50 of the dose-response curves for quisqualate. Responses to both agonists were antagonised by kynurenic acid, barbiturates and gamma-DGT to a similar extent. The antagonism by kynurenate appeared to be competitive whilst the barbiturates were evidently noncompetitive antagonists. These results are in agreement with claims that quisqualate and AMPA act at a similar recognition site. The differences in the slopes of the dose-response curves for quisqualate and AMPA may be explained by the differences in the cellular uptake of the two agonists and/or by differences in efficacy.
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http://dx.doi.org/10.1016/0028-3908(89)90125-1 | DOI Listing |
Molecules
October 2020
Department of Nuclear Medicine, University of Bern, Inselspital, Freiburgstrasse 18, CH-3010 Bern, Switzerland.
Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases.
View Article and Find Full Text PDFFront Neurosci
September 2020
Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, United States.
The neurotoxic action of glutamic acid was first described by Lucas and Newhouse, who demonstrated neural degeneration in the inner layers of the neonatal mouse retina after systemic treatment with L-glutamate. Olney extended these findings by showing that neuronal degeneration affected other brain structures including neurons within the arcuate nucleus of the hypothalamus and the area postrema, that the lesion spared axons passing through these areas, and that the neurotoxic potency of glutamate analogs correlated with their excitatory potency, resulting in the designation "excitotoxins." As this method affected only a small number of brain regions, it was not suitable for targeted brain lesions.
View Article and Find Full Text PDFBiomolecules
October 2019
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Perampanel (PER) is a selective blocker of AMPA receptors showing efficacy in treating various epileptic disorders including brain tumor-related epilepsy and also potential in treating motor neuron disease. However, besides its inhibition of AMPA-induced currents, whether PER has any other direct ionic effects in different types of neurons remains largely unknown. We investigated the effects of PER and related compounds on ionic currents in different types of cells, including hippocampal mHippoE-14 neurons, motor neuron-like NSC-34 cells and U87 glioma cells.
View Article and Find Full Text PDFPharm Biol
December 2019
b Photon Medical Research Center , Hamamatsu University School of Medicine, Hamamatsu , Japan.
Context: Fucoidan, a sulphated polysaccharide extracted from brown algae [Fucus vesiculosus Linn. (Fucaceae)], has multiple biological activities.
Objective: The effects of fucoidan on Ca responses of rat neurons and its probable mechanisms with focus on glutamate receptors were examined.
IUCrJ
November 2018
Biostructural Research, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
The AMPA receptor GluA2 belongs to the family of ionotropic glutamate receptors, which are responsible for most of the fast excitatory neuronal signalling in the central nervous system. These receptors are important for memory and learning, but have also been associated with brain diseases such as Alzheimer's disease and epilepsy. Today, one drug is on the market for the treatment of epilepsy targeting AMPA receptors, a negative allosteric modulator of these receptors.
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