Activation of glutamate uptake by guanosine in primary astrocyte cultures

Guanine-based purines have been shown to modulate the effects of glutamate, which is essential for brain function and mediates excitotoxicity. In the search for a mechanism involving the interaction between purine nucleoside guanosine and glutamate, we found that guanosine dose-dependently, signific antly (63%) and potently (EC50 = 2.47 muM) enhanced glutamate uptake in cul tured astrocytes. This effect was not inhibited by the blocker of nucleosid e transporter dipyridamole nor by the adenosine antagonist theophylline, su ggesting an extracellular site of action without the involvement of adenosi ne receptors. These results indicate a regulatory role of guanosine on extr acellular levels of glutamate, possibly contributing for protecting neural cells against glutamate-induced excitotoxicity. NeuroReport 12:879-881 (C) 2001 Lippincott Williams & Wilkins.