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Titolo:
Enhancement of NMDA-induced current by the putative NR2B selective antagonist ifenprodil
Autore:
Zhang, XX; Bunney, BS; Shi, WX;
Indirizzi:
Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 , Dept Psychiat, New Haven, CT 06520 USA
Titolo Testata:
SYNAPSE
fascicolo: 1, volume: 37, anno: 2000,
pagine: 56 - 63
SICI:
0887-4476(200007)37:1<56:EONCBT>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
D-ASPARTATE RECEPTOR; PREFRONTAL CORTEX; CORTICAL-NEURONS; EXPRESSION; DOPAMINE; SUBUNIT; POLYAMINE; SUBTYPES; CHANNEL; SITE;
Keywords:
ifenprodil; NMDA; NR2B; prefrontal cortex; pyramidal cell; brain slice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Shi, WX Yale Univ, Sch Med, Dept Psychiat, 333 Cedar St,SHM B-272,POB 208066, New Haven, CT 06520 USA Yale Univ 333 Cedar St,SHM B-272,POB 208066 NewHaven CT USA 06520
Citazione:
X.X. Zhang et al., "Enhancement of NMDA-induced current by the putative NR2B selective antagonist ifenprodil", SYNAPSE, 37(1), 2000, pp. 56-63

Abstract

Ifenprodil has been widely used as an antagonist selective for NMDA receptors containing the NR2B subunit. Evidence suggests, however, that ifenprodil also increases NMDA receptor affinity. Using rat brain slices, we found that ifenprodil enhanced NMDA-induced current in both cortical and subcortical areas examined. To test whether the effect is due to an increase in NMDAreceptor affinity, we compared the effect of ifenprodil on currents induced by different concentrations of NMDA. Consistent with the hypothesis, the enhancing effect (percent increase) was relatively constant at low NMDA concentrations. As NMDA concentration increased, however the effect decreased. To test whether the effect is blocked when NMDA binding sites are saturated with NMDA, high concentrations of NMDA were applied. To partially block Ca2+ influx and prevent cells fi om deteriorating, the experiments were performed in the presence of either MK801 or kynurenate, two noncompetitive antagonists. Under such conditions, ifenprodil not only failed to potentiate NMDA currents, but consistently suppressed the current. When the same concentration of NMDA was applied in the presence of the competitive antagonist CGP37849, ifenprodil regained its ability to potentiate NMDA currents. Furthermore, the higher the concentration of CGP37849 the more the NMDA current was potentiated by ifenprodil. These results, combined with previous studies, suggest that the enhancing effect is due to an increase in NMDA receptoraffinity and is specific for responses induced by low NMDA concentrations. As NMDA concentration increases, the affinity-enhancing effect decreases. Consequently, the channel-suppressing effect becomes more prominent. (C) 2000 Wiley-Liss, Tnc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 19:11:10