Proposal of a guanine-based purinergic system in the mammalian central nervous system

Guanine-based purines have been traditionally studied as modulators of intracellular processes, mainly G-protein activity. However, they also exert several extracellular effects not related to G proteins, including modulation of glutamatergic activity, trophic effects on neural cells, and behavioral effects. In this article, the putative roles of guanine-based purines on the nervous system are reviewed, and we propose a specific guanine-based purinergic system in addition to the well-characterized adenine-based purinergic system. Current evidence suggest that guanine-based purines modulate glutamatergic parameters, such as glutamate uptake by astrocytes and synaptic vesicles, seizures induced by glutamatergic agents, response to ischemia and excitotoxicity, and are able to affect learning, memory and anxiety. Additionally, guanine-based purines have important trophic functions affecting the development, structure, or maintenance of neural cells. Although studies addressing the mechanism of action (receptors and second messenger systems) of guanine-based purines are still insufficient, these findings point to the guanine-based purines (nucleotides and guanosine) as potential new targets for neuroprotection and neuromodulation.