Specific [³H]‐guanosine binding sites in rat brain membranes

Abstract

1 Extracellular guanosine has diverse e ects on many cellular components of the central nervous system, some of which may be related to its uptake into cells and others to its ability to release adenine-based purines from cells. Yet other e ects of extracellular guanosine are compatible with an action on G-protein linked cell membrane receptors. 4 This site was speci®c for guanosine, and the order of potency in displacing 50 nM [ 3 H]-guanosine was: guanosine=6-thio-guanosine4inosine46-thio-guanine4guanine. Other naturally occurring purines, such as adenosine, hypoxanthine, xanthine ca eine, theophylline, GDP, GMP and ATP were unable to signi®cantly displace the radiolabelled guanosine. Thus, this binding site is distinct from the well-characterized receptors for adenosine and purines. 5 The addition of GTP produced a small concentration-dependent decrease in guanosine binding, suggesting this guanosine binding site was linked to a G-protein.

Guanosine prevents nitroxidative stress and recovers mitochondrial membrane potential disruption in hippocampal slices subjected to oxygen/glucose deprivation

“…GUO prevents the decrease in cell viability, by increasing glutamate uptake and glutamine synthetase activity, decreasing glutamate release, ROS production and inflammatory mediators expression, including reduction of iNOS expression [14,15,33,40]. The exact interaction site of GUO in cellular membranes is still unknown, although it has been suggested [41,42]. GUO effects over adenosinergic system are controversial [43], but we have shown that neuroprotective effects of GUO depend on adenosine receptors modulation [33] and on activation of a calcium-dependent potassium channel [14].…”

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

“…It is also conceivable that Urd, Guo, and Ade have their own receptors (UrdR, GuoR, AdeR, respectively; Fig. 29.1 ) that are used to execute certain functions in the nervous system (Bender et al 2002 ;Borrmann et al 2009 ;Kimura et al 2001 ;Schulte and Fredholm 2003 ;Traversa et al 2002 ) .…”

Intranasal guanosine administration presents a wide therapeutic time window to reduce brain damage induced by permanent ischemia in rats

“…A putative binding site for GUO was already described in rat brain membranes [17], but in opposite, several evidences point to an adenosine (ADO) receptors contribution for GUO effects. Indeed, some, but not all of the observed neuroprotective effects of GUO, were blocked by ADO receptor antagonists, suggesting multiple mechanisms of action for GUO [18][19][20][21][22].…”