Guanine nucleotides inhibit NMDA and kainate-induced neurotoxicity in cultured rat hippocampal and neocortical neurons

Neurotoxicity Induced by Glutamate in Glucose-Deprived Rat Hippocampal Slices is Prevented by GMP

“…Considering that carriers to phosphorylated nucleotides in the plasmatic membrane were not yet demonstrated, the mechanism of action of GMP as a neuroprotective agent could be related to its ability to act as a glutamate receptor antagonist. Accordingly, the neuroprotective effects of GMP in hippocampal slices (21) and neuronal cultures (35) were similar to the effects observed with classical glutamate receptors antagonists. On the contrary, guanosine added to neuronal cultures displayed a protective role only if the enzyme responsible for its hydrolysis was not inhibited (36), indicating that the neuroprotective effect of guanosine would also be exerted by providing intermediates to maintain cell metabolism.…”

“…However, we have previously reported that GMP per se inhibits cellular responses induced by glutamate (12,13). Moreover, guanine nucleotides inhibit NMDA and Kainate-induced neurotoxicity in cultured neurons (35). Here we are showing that extracellular added GMP prevented the damage induced by glucose deprivation in the presence of glutamatergic agonists.…”

An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration

“…Excessive activation of glutamate receptor systems is implicated in neuronal cell death associated with stroke and neurodegenerative diseases such as AD, PD, HD and ALS (Zona et al, 2000). Guanine nucleotides inhibit N-methyl-D-aspartate (NMDA)-and kainateinduced neurotoxicity and may be used to antagonise glutamate receptor-mediated neurotoxicity (Morciano et al, 2004). The P1 receptor antagonist, caffeine, is claimed to have beneficial actions in both AD and PD (Ribeiro et al, 2003).…”

Pathophysiology and Therapeutic Potential of Purinergic Signaling

“…Release of ATP from disrupted cells may cause cell death in neighboring cells expressing P2X 7 receptors, leading to a necrotic volume increase, which has been proposed as a cellular mechanism in the pathogenesis of Parkinson's disease (Jun and Kim, 2004). Guanine nucleotides inhibit NMDA and kainate-induced neurotoxicity in cultured rat hippocampal and neocortical neurons and may be candidates for antagonizing glutamate receptor-mediated neurotoxicity (Morciano et al, 2004). P2 receptors have been claimed to mediate neuroprotective effects in the cerebellum and the possible therapeutic use of P2 receptor agonists as neuroprotective agents has been raised (Volonte et al, 1999(Volonte et al, , 2003.…”