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Titolo:
The non-NMDA glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline, but not NMDA antagonists, block the intrastriatal neurotoxic effect of MPP+
Autore:
Merino, M; Vizuete, ML; Cano, J; Machado, A;
Indirizzi:
Univ Sevilla, Fac Farm, Dept Bioquim Bromatol & Toxicol, E-41012 Seville, Spain Univ Sevilla Seville Spain E-41012 tol & Toxicol, E-41012 Seville, Spain
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 2, volume: 73, anno: 1999,
pagine: 750 - 757
SICI:
0022-3042(199908)73:2<750:TNGRA6>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
1-METHYL-4-PHENYLPYRIDINIUM ION MPP+; D-ASPARTATE ANTAGONISTS; PARKINSONS-DISEASE; BASAL GANGLIA; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; KYNURENIC ACID; MK-801 FAILS; RAT; PROTECTION;
Keywords:
MPP+; rat striatum; dopaminergic neuroprotection; kynurenic acid; dizocilpine; 6-cyano-7-nitroquinoxaline-2,3-dione; 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Machado, A Univ Sevilla, Fac Farm, Dept Bioquim Bromatol & Toxicol, Calle Prof GarciaGonzalez S-N, E-41012 Seville, Spain Univ Sevilla Calle Prof Garcia Gonzalez S-N Seville Spain E-41012
Citazione:
M. Merino et al., "The non-NMDA glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline, but not NMDA antagonists, block the intrastriatal neurotoxic effect of MPP+", J NEUROCHEM, 73(2), 1999, pp. 750-757

Abstract

Altered glutamatergic neurotransmission appears to be central to the pathophysiology of Parkinson's disease; consequently, considerable effort has been made to elucidate neuroprotective mechanisms against such toxicity. In the present study, the possible neuroprotective effect of glutamate receptorantagonists against MPP+ neurotoxicity on dopaminergic terminals of rat striatum was investigated. Different doses of glutamate receptor antagonists were coinfused with 1.5 mu g of MPP+ into the striatum; kynurenic acid, a nonselective antagonist of glutamate receptors (30 and 60 nmol), partially protected dopaminergic terminal degeneration in terms of rescue of dopamine levels and tyrosine hydroxylase immunohistochemistry. Dizocilpine, a channel blocker of the NMDA receptor (1, 4, and 8 nmol), and 7-chlorokynurenic acid, a selective antagonist at the glycine site of the NMDA receptor (1 and 10 nmol), failed to protect dopaminergic terminals from MPP+ toxicity. However, 6-cyano-7-nitroquinoxaline-2,3-dione (0.5 and 1 nmol) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (1 nmol), two AMPA-kainate receptor antagonists, protected against MPP+ toxicity. Our findings suggest that the toxic effects of MPP+ on dopaminergic terminals are not mediated througha direct interaction with the NMDA subtype of glutamate receptor, but withthe AMPA-kainate subtype.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 07:07:38