Guanosine Enhances Glutamate Uptake in Brain Cortical Slices at Normal and Excitotoxic Conditions

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Abstract
1. The effect of guanosine on L-[2,3-3H]glutamate uptake was investigated in brain cortical slices under normal or oxygen–glucose deprivation (OGD) conditions. 2. In slices exposed to physiological conditions, guanosine (1–100 μM) stimulated glutamate uptake (up to 100%) in a concentration-dependent manner when a high (100 μM) but not a low (1 μM) concentration of glutamate was used. 3. In slices submitted to OGD, guanosine 1 and 100 μM also increased 100 μM glutamate uptake (38 and 70%, respectively). 4. The increasing of glutamate and taurine released to the incubation medium in cortical slices submitted to OGD were significantly attenuated by the presence of guanosine in the incubation medium. 5. Guanosine prevented the increase in propidium iodide incorporation into cortical slices induced by OGD, indicating a protective role against ischemic injury. 6. These results support the hypothesis of a protective role for guanosine during brain ischemia, possibly by activating glutamate uptake into neural cells.