Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Specific glutathione binding sites in pig cerebral cortical synaptic membranes
Autore:
Janaky, R; Shaw, CA; Varga, V; Hermann, A; Dohovics, R; Saransaari, P; Oja, SS;
Indirizzi:
Univ Tampere, Sch Med, Tampere Brain Res Ctr, FIN-33101 Tampere, Finland Univ Tampere Tampere Finland FIN-33101 s Ctr, FIN-33101 Tampere, Finland Univ British Columbia, Dept Ophthalmol, Vancouver, BC, Canada Univ BritishColumbia Vancouver BC Canada thalmol, Vancouver, BC, Canada Lajos Kossuth Univ, Dept Anim Physiol, Debrecen, Hungary Lajos Kossuth Univ Debrecen Hungary ept Anim Physiol, Debrecen, Hungary Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland Tampere Univ Hosp Tampere Finland , Dept Clin Physiol, Tampere, Finland
Titolo Testata:
NEUROSCIENCE
fascicolo: 2, volume: 95, anno: 2000,
pagine: 617 - 624
SICI:
0306-4522(2000)95:2<617:SGBSIP>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN; H-3 GLUTATHIONE; D-ASPARTATE; ENDOGENOUS AGONIST; AMPA RECEPTORS; L-CYSTEINE; GLUTAMATE; ACID; NMDA; SYNAPTOSOMES;
Keywords:
glutathione binding; glutamate receptors; cerebral cortical membranes; pig;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Janaky, R Univ Tampere, Sch Med, Tampere Brain Res Ctr, Box 607, FIN-33101Tampere, Finland Univ Tampere Box 607 Tampere Finland FIN-33101 Tampere, Finland
Citazione:
R. Janaky et al., "Specific glutathione binding sites in pig cerebral cortical synaptic membranes", NEUROSCIENC, 95(2), 2000, pp. 617-624

Abstract

Glutathione (gamma-glutamylcysteinylglycine) is a neuromodulator at glutamate receptors, but may also act as a neurotransmitter at sites of its own. The Na+-independent binding of [H-3]glutathione to pig cortical synaptic membranes was characterized here using glycine, cysteine analogs, dipeptides and glutathione derivatives, and ligands selective for known glutamate receptors. L-Glutamate, pyroglutamate, quinolinate, (S)-5-fluorowillardiine and6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3 dione were weak inhibitors at concentrations of 0.5 or 1 mM. D-Glutamate, L- and D-aspartate, glutamine, quisqualate, kynurenate, other N-methyl-D-aspartate receptor ligands and non-N-methyl-D-aspartate receptor Ligands failed to displace [3H]glutathione. Except for weak inhibition by D-serine (0.5 mM), glycine and other ligands of the glycine co-activatory site in the N-methyl-D-aspartate receptors hadno displacing effect. Similarly, metabotropic glutamate group I, II and III receptor agonists and antagonists and compounds acting at the glutamate uptake sites were generally inactive. Glutathione, oxidized glutathione, S-nitrosoglutathione, gamma-L-glutamylcysteine, cysteinylglycine, cysteine, cysteamine and cystamine were the most potent displacers (IC50 values in the micromolar range), followed by dithiothreitol, glutathione sulfonate and the S-alkyl derivatives of glutathione (S-methyl-, -ethyl-, -propyl-, -butyl-and -pentylglutathione). L-Homocysteinate and aminomethanesulfonate exhibited a moderate efficacy. Thiokynurenate, a cysteine analog and an antagonist at the N-methyl-D-aspartate receptor glycine co-activatory site, was a potent activator of glutathione binding. At 1 mM, some dipeptides also slightly activated the binding, gamma-L-glutamylleucine and delta-L-glutamyl-GABAbeing the most effective. The specific binding sites for glutathione in brain synaptic membranes are not identical to any known excitatory amino acidreceptor. The cysteinyl moiety is crucial in the binding of glutathione. The oxidation or alkylation of the cysteine thiol group reduces the binding affinity. The strong activation by thiokynurenate may indicate that the glutathione receptor protein contains a modulatory site to which co-agonists may bind and allosterically activate glutathione binding. The novel population of specific binding sites of glutathione gives rise to the possibility that they may have profound effects on synaptic functionsin the mammalian central nervous system. The glutathione binding sites maybe an important, and for the most part unrecognized, component in signal transduction in the brain. (C) 1999 IBRO. Published by Elsevier Science Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 08:38:24