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Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells

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Palmada,  Mònica
Max Planck Institute of Molecular Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons98704

Kinne-Saffran,  Evamaria
Sonstige Wissenschaftliche Organisationseinheiten, Max Planck Institute of Molecular Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons98705

Kinne,  Rolf K.H.
Sonstige Wissenschaftliche Organisationseinheiten, Max Planck Institute of Molecular Physiology, Max Planck Society;

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Citation

Palmada, M., Kinne-Saffran, E., Centelles, J. J., & Kinne, R. K. (2002). Benzodiazepines differently modulate EAAT1/GLAST and EAAT2/GLT1 glutamate transporters expressed in CHO cells. Neurochemistry International, 40(4): 1, pp. 321-326. Retrieved from http://dx.doi.org/10.1016/S0197-0186(01)00087-0.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-0E91-6
Abstract
It has been described recently that low concentrations of benzodiazepines stimulate the transport activity of the neuronal glutamate transporter EAAT3, whereas high concentrations inhibit it. The present study is aimed to investigate whether benzodiazepines have similar effects on the two glial glutamate transporter, EAAT1 and EAAT2. To this end, the transporters were transiently expressed in CHO cells and transport activity was determined by isotope fluxes using D- aspartate as non-metabolizable homologue Of L-glutamate. At low D-aspartate concentrations (1 mumol/l) EAAT1-mediated uptake was reduced significantly by low concentrations of oxazepam (1 mumol/l) and diazepam (1 and 10 mumol/l). At 100 mumol/l D- aspartate oxazepam stimulated EAAT1-mediated uptake up to 150% in a dose dependent manner, whereas the inhibition by low concentrations of diazepam was attenuated. In contrast, a significant effect of diazepam on EAAT2-mediated uptake was only observed at 1000 mumol/l where uptake was inhibited by 60%. A similar inhibition was observed for EAAT1. These studies demonstrate a different modulation of EAAT1 and EAAT2 by benzodiazepines. Furthermore the glial transporters differ from the neuronal glutamate transporter. Thus, a complex in vivo response of the various transporters to benzodiazepines can be expected. (C) 2002 Elsevier Science Ltd. All rights reserved.