Guanosine enhances glutamate uptake in brain cortical slices at normal and excitotoxic conditions.
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 microM) stimulated glutamate uptake (up to 100%) in a concentration-dependent manner when a high (100 microM) but not a low (1 microM) concentration of glutamate was used. 3. In slices submitted to OGD, guanosine 1 and 100 microM also increased 100 microM 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.
Frizzo
Marcos Emílo dos Santos
ME
Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. frizzo@vortex.ufrgs.br
Lara
Diogo Rizzato
DR
Prokopiuk
Alexandre de Souza
Ade S
Vargas
Carmen Regla
CR
Salbego
Christianne Gazzana
CG
Wajner
Moacir
M
Souza
Diogo Onofre
DO
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006151:Guanosine / Q000378:metabolism / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009498:Neurotoxins / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism; D013654:Taurine / Q000378:metabolism
D018696:Neuroprotective Agents; D009498:Neurotoxins; D006151:Guanosine; D013654:Taurine; D018698:Glutamic Acid