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Titolo:
CHARACTERIZATION OF CYCLOTHIAZIDE-ENHANCED KAINATE EXCITOTOXICITY IN RAT HIPPOCAMPAL CULTURES
Autore:
OHNO K; OKADA M; TSUTSUMI R; MATSUMOTO N; YAMAGUCHI T;
Indirizzi:
YAMANOUCHI PHARMACEUT CO LTD,INST DRUG DISCOVERY RES,NEUROSCI RES PHARMACOL LABS,21 MIYUKIGAOKA TSUKUBA IBARAKI 305 JAPAN
Titolo Testata:
Neurochemistry international
fascicolo: 3, volume: 32, anno: 1998,
pagine: 265 - 271
SICI:
0197-0186(1998)32:3<265:COCKEI>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID RELEASE; RECEPTOR DESENSITIZATION; GLUTAMATE NEUROTOXICITY; AMPA RECEPTORS; CONCANAVALIN-A; NEURONS; MODULATION; CURRENTS; INVITRO; BINDING;
Keywords:
CYCLOTHIAZIDE; KAINATE; AMPA; NMDA; HIPPOCAMPUS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
25
Recensione:
Indirizzi per estratti:
Citazione:
K. Ohno et al., "CHARACTERIZATION OF CYCLOTHIAZIDE-ENHANCED KAINATE EXCITOTOXICITY IN RAT HIPPOCAMPAL CULTURES", Neurochemistry international, 32(3), 1998, pp. 265-271

Abstract

Cyclothiazide has been shown to block desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-preferring receptors and to enhance quisqualate-, AMPA- and kainate-induced neurotoxicity. The pharmacology behind this cyclothiazide-enhanced kainate-induced excitotoxicity was characterized in embryonic rat hippocampal cell cultures. Treatment of cell cultures with a combination of cyclothiazide and kainate for 24 h resulted in excessive neuronal death as measured by the release of lactate dehydrogenase into the culture media. Cyclothiazide produced a leftward shift of the kainate dose-response curveand enhanced the maximum response of kainate excitotoxicity. AMPA-preferring receptor antagonists, dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX) and -4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466) blocked cyclothiazide-enhanced kainate toxicity completely, and cyclothiazide increased the IC(50)s for NBQX and GYKI 52466 against kainate toxicity. The N-methyl-D-aspartate (NMDA) antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine (MK801) also blocked cyclothiazide-enhanced kainate toxicity, but only partially. Cyclothiazide also increased the IC50 for MK801 against kainate toxicity. These data suggest that cyclothiazide enhances both AMPA-preferring receptor-and NMDA receptor-mediated toxicity in kainate-induced toxicity in embryonic rat hippocampal cultures. (C) 1998 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 13:31:10