NDLI: Terfenadine induces toxicity in cultured cerebellar neurons: A role for glutamate receptors

Content Provider	Springer Nature Link
Author	Díaz Trelles, R. Solana López, A. Fernández González, J. R. velli, Antonello Fernández Sánchez, María Teresa
Copyright Year	1999
Abstract	Exposure of cultured cerebellar neurons to the histamine H1 receptor antagonist terfenadine resulted in neuronal degeneration and death. Terfenadine neurotoxicity was dependent upon concentration and time of exposure. After 2h exposure, 20µM terfenadine reduced the number of surviving neurons by 75%, and as low as 10nM terfenadine induced significant neurotoxicity after 5 days of exposure. Neuronal sensitivity to terfenadine changed with age in culture, and at 25 days in culture neurons appeared to be much less sensitive than at 5 or 9–17 days in culture. Neurotoxicity by terfenadine could not be prevented by high concentrations of histamine (5 mM), but it was significantly delayed by blocking NMDA or non-NMDA glutamate receptors with MK-801 or CNQX respectively, suggesting the involvement of excitatory transmission mediated by glutamate in the neurotoxicity induced by terfenadine in these neurons. We also found that the presence of terfenadine (5,µM) unveiled the potential excitotoxicity of the non-NMDA receptor agonist AMPA (100µM), and reduced the concentration of glutamate necessary to induce excitotoxicity, compared to untreated cultures. These results suggest a role for terfenadine in the modulation of the excitotoxic response mediated in cerebellar neurons through ionotropic glutamate receptors.
Starting Page	59
Ending Page	70
Page Count	12
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	16
Issue Number	1
e-ISSN	14382199
Language	English
Publisher	Springer-Verlag
Publisher Date	1999-01-01
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Amino acids Cerebellar granule cells Neurotoxicity Terfenadine Excitatory amino acids Histamine Analytical Chemistry Biochemical Engineering Life Sciences Biochemistry Proteomics Neurobiology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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