Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
QUINOLINATE POTENTIATES THE NEUROTOXICITY OF EXCITATORY AMINO-ACIDS IN HYPOXIC NEURONAL TISSUE IN-VITRO
Autore:
SCHURR A; RIGOR BM;
Indirizzi:
UNIV LOUISVILLE,SCH MED,DEPT ANESTHESIOL LOUISVILLE KY 40292
Titolo Testata:
Brain research
fascicolo: 1, volume: 617, anno: 1993,
pagine: 76 - 80
SICI:
0006-8993(1993)617:1<76:QPTNOE>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; HIPPOCAMPAL SLICE PREPARATION; 7-CHLOROKYNURENIC ACID; HUNTINGTONS-DISEASE; CEREBROSPINAL-FLUID; CULTURED NEURONS; NERVOUS-SYSTEM; BRAIN; GLUTAMATE; COMPLEX;
Keywords:
HIPPOCAMPAL SLICE; HYPOXIA; KA/AMPA RECEPTOR; NMDA RECEPTOR; POTENTIATION OF NEURONAL DAMAGE; QUINOLINATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
A. Schurr e B.M. Rigor, "QUINOLINATE POTENTIATES THE NEUROTOXICITY OF EXCITATORY AMINO-ACIDS IN HYPOXIC NEURONAL TISSUE IN-VITRO", Brain research, 617(1), 1993, pp. 76-80

Abstract

Excitatory amino acids (EAAs) in the central nervous system are involved in both neurotransmission and neurotoxicity. Quinolinate (QUIN) isa neurotoxic endogenous tryptophan metabolite that has been linked toHuntington's disease, Alzheimer's disease, and many inflammatory diseases. We used the rat hippocampal slice preparation and its electrophysiology to study the interaction of QUIN with glutamate receptor agonists such as N-methyl-D-aspartate (NMDA), glutamate, aspartate, kainate, and AMPA R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepro pionate). The majority of slices could tolerate an exposure to 10-min hypoxia (86% recovered their neuronal function), but doses of glutamate receptor agonists which were harmless under normoxic conditions, significantly reduced this recovery rate under hypoxic conditions. QUIN, at dosesthat even under hypoxic conditions were innocuous (20-50 muM), potentiated the neurotoxic effects of all the glutamate receptor agonists tested in hypoxic hippocampal slices. The NMDA antagonist D,L-2-amino-5-phosphonovalerate blocked this potentiation while 7-chloro-kynurenate,at a dose sufficient to block the effect of NMDA alone, was ineffective in blocking the potentiation of NMDA toxicity by QUIN. Non-toxic analogues of QUIN (6-methyl-QUIN and 2,3-pyrazine dicarboxylate) were also able to potentiate NMDA toxicity in hypoxic slices. The results of these experiments provided indirect evidence that QUIN is an endogenous potentiator of the NMDA and the kainate receptor subtypes; therefore, we postulate that QUIN has a specific modulatory binding site on allglutamate receptor subtype complexes. Regardless of its site of interaction, the importance of QUIN as a potentiator of the agonistic activation of these receptors cannot be overemphasized. Thus. the in vivo involvement of QUIN in increasing the neurotoxic efficacy of EAAs in brain disorders such as cerebral ischemia should be considered.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 10:22:15