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Titolo:
S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effectagainst N-methyl-D-aspartate receptor-mediated neurotoxicity
Autore:
Ningaraj, NS; Chen, WQ; Schloss, JV; Faiman, MD; Wu, JY;
Indirizzi:
Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA Univ Kansas LawrenceKS USA 66045 Dept Mol Biosci, Lawrence, KS 66045 USA Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA Univ KansasLawrence KS USA 66045 macol & Toxicol, Lawrence, KS 66045 USA Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA Univ Kansas Lawrence KS USA 66045 , Dept Med Chem, Lawrence, KS 66045 USA
Titolo Testata:
JOURNAL OF BIOMEDICAL SCIENCE
fascicolo: 1, volume: 8, anno: 2001,
pagine: 104 - 113
SICI:
1021-7770(200101/02)8:1<104:SSENE>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ETHANOL WITHDRAWAL SEIZURES; ACUTE AMMONIA TOXICITY; GATED ION CHANNELS; NMDA RECEPTOR; N,N-DIETHYLTHIOLCARBAMATE SULFOXIDE; ALDEHYDE DEHYDROGENASE; GLUTAMATE RECEPTORS; ALCOHOL INTAKE; RAT; DISULFIRAM;
Keywords:
S-methyl-N,N-diethylthiocarbamate sulfoxide disulfiram; N-methyl-D-aspartate receptor; alcoholism; neurotoxicity; anticraving agent;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Wu, JY Univ Kansas, Dept Mol Biosci, 1043 Haworth Hall, Lawrence, KS 66045USA Univ Kansas 1043 Haworth Hall Lawrence KS USA 66045 e, KS 66045 USA
Citazione:
N.S. Ningaraj et al., "S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effectagainst N-methyl-D-aspartate receptor-mediated neurotoxicity", J BIOMED SC, 8(1), 2001, pp. 104-113

Abstract

Glutamatergic neurotransmission, particularly of the NMDA receptor type, has been implicated in the excitotoxic response to several external and internal stimuli. In the present investigation, we report that S-methyl-N,N-diethyithiocarbamate sulfoxide (DETC-MeSO) selectively and specifically blocksthe NMDA receptor subtype of the glutamate receptors, and attenuates glutamate-induced neurotoxicity in rat-cultured primary neurons. Other major ionotropic glutamate receptor subtypes, alpha -amino-3-hydroxy-5-methyt-4-isoxazolepropionic acid and kainate, were insensitive to DETC-MeSO both in vitro and in vivo. Disulfiram, the parent compound of DETC-MeSO, also inhibits glutamate receptors partially in vivo; however, it fails to inhibit glutamate receptors in mice pretreated with N-butyl imidazole, a cytochrome P450 enzyme inhibitor, implicating the need for bioactivation of disulfiram to bean effective antagonist. We showed that glutamate-induced increase in Ca-45(2+) was attenuated in rat-cultured primary neurons following pretreatmentwith DETC-MeSO. The Ca2+ influx into primary neurons, studied by confocal microscopy of the fluorescent Ca2+ dye fura-2, demonstrated a complete attenuation of NMDA-induced Ca2+ influx. Similarly, DETC-MeSO attenuated NMDA-induced Ca-45(2+) uptake. Glutamate-induced Ca-45(2+) uptake and Ca2+ influx, however, were partially blocked by DETC-MeSO, and this is consistent withboth in vitro and in vivo studies in which DETC-MeSO partially blocked mouse brain glutamate receptors. In addition, DETC-MeSO pretreatment effectively prevented seizures in mice induced either by NMDA, ammonium acetate, or ethanol-induced kindling seizures, all of which are believed to be mediatedby NMDA receptors. These data demonstrate that DETC-MeSO produces the neuroprotective effect through antagonism of NMDA receptors in vivo. Copyright (C) 2001 National Science Council, ROC and S. Karger AG, Basel.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 00:02:13