Adenosine A1 and A2A receptors are involved on guanosine protective effects against oxidative burst and mitochondrial dysfunction induced by 6-OHDA in striatal slices

Dynamic and Rapid Detection of Guanosine during Ischemia

“…This behavior is indicative of the negative feedback effects of an inhibitory autoreceptor with a high activation threshold. Guanosine is currently considered an orphan neuromodulator; while significant evidence for a guanosine-specific receptor has been established, the precise receptor has yet to be identified. , Adenosine’s A 1 receptor is well known for its inhibitory effects and has been demonstrated to negatively regulate rapid adenosine release. − Guanosine can interact nonspecifically at the A 1 receptor to activate a variety of neuroprotective pathways; however, abolition of adenosine receptors does not fully abolish guanosine’s protective impact, suggesting a role for its individual receptor. ,, …”

“…Guanosine administration also lowers microglial activation and decreases inflammatory cytokine levels after injury. ,− On a molecular level, guanosine is intimately entwined with several essential neurochemical responses to injury. Guanosine administration lowers accumulation of reactive oxygen species and decreases oxidative stress in a variety of pathological models. ,, It facilitates increased glutamate clearance from the extracellular space, an essential role for minimizing the effects of glutamatergic excitotoxicity during ischemia, and can decrease membrane permeability through antagonistic binding at NMDA receptors. ,− Guanosine is also involved in the broader purinergic response to ischemia. Extracellular adenosine levels rise rapidly following guanosine administration, and guanosine interacts at adenosine receptors involved in cell recovery pathways. ,, While guanosine’s importance is clear, no study has examined guanosine’s endogenous response at the point and time of ischemic assault.…”

“…Guanosine administration lowers accumulation of reactive oxygen species and decreases oxidative stress in a variety of pathological models. 19,29,30 It facilitates increased glutamate clearance from the extracellular space, an essential role for minimizing the effects of glutamatergic excitotoxicity during ischemia, and can decrease membrane permeability through antagonistic binding at NMDA receptors. 16,31−35 Guanosine is also involved in the broader purinergic response to ischemia.…”

“…Extracellular adenosine levels rise rapidly following guanosine administration, and guanosine interacts at adenosine receptors involved in cell recovery pathways. 30,36,37 While guanosine's importance is clear, no study has examined guanosine's endogenous response at the point and time of ischemic assault. Although guanosine is known to be a potent neuromodulator, its ability to respond rapidly and dynamically has gone uninvestigated.…”

Neuroprotection afforded by targeting G protein-coupled receptors in heteromers and by heteromer-selective drugs

“…Another homotropic heteromer, formed by adenosine A 1 and A 2A receptors seems to be involved in the in vitro neuroprotective potential of an endogenous nucleoside, guanosine (Massari et al, 2021). The in vitro benefits of guanosine, consists of reducing both mitochondrial alterations and oxidative stress.…”