NMDA receptor dependent and independent components of veratridine toxicity in cultured cerebellar neurons are prevented by nanomolar concentrations of terfenadine

被引:6
作者
Díaz-Trelles, R
Novelli, A [1 ]
Puia, G
Baraldi, M
Fernández-Sánchez, MT
机构
[1] Univ Oviedo, Fac Med, Dept Bioquim & Biol Mol, E-33071 Oviedo, Spain
[2] Univ Oviedo, Dept Psychol, Oviedo, Spain
[3] Univ Modena, Dept Pharmaceut Sci, I-41100 Modena, Italy
关键词
amino acids; glutamate release; excitotoxicity; terfenadine; sodium channels;
D O I
10.1007/s007260070057
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Exposure of cultured neurons to nanomolar concentrations of terfenadine prevented the NMDA receptor-mediated early appearance (30min.) of toxicity signs induced by the voltage sensitive sodium channel activator veratridine. Terfenadine also provided an histamine-insensitive protection against delayed neurotoxicity by veratridine (24h), occurring independently of NMDA receptor activation, while not protecting from excitotoxicity following direct exposure of neurons to glutamate. Terfenadine reduced tetrodotoxin-sensitive inward currents, and reduced intracellular cGMP formation following veratridine exposure. Our data suggest that nanomolar concentrations of TEF may reduce excitatory aminoacid release following neuronal depolarization via a presynaptic mechanism involving voltage sensitive sodium channels, and therefore may be considered as a prototype for therapeutic drugs in the treatment of diseases that involve excitatory aminoacid neurotransmission.
引用
收藏
页码:263 / 272
页数:10
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