Several studies have shown that guanine-based purines exert biological effects, possibly through membrane receptor, but at the present there are no reports related to the identification of such specific receptor(s). In the present study, using an human glioma cell line (U87), we report that the silencing of G protein-coupled receptor GPR23, also known as LPA4 receptor, reduces significantly the antiproliferative effects of guanosine, while stably transfected cell clones over-expressing GPR23 increases sensitivity to guanosine. [³H] Guanosine radioligand binding assay revealed that [³H]-Guanosine binding to membrane fractions was greatly enhanced by GPR23 overexpression, and inhibited by GPR23 silencing (K_D=59.5 nM and B_max=809.5 fmol mg^-1 protein in U87 GPR23-overexpressing cells (K_D=43.8 nM and B_max=499.5 fmol mg^-1 protein in U87 wt cells and a K_D=54.1 nM and B_max= 336.7 fmol mg^-1 protein in U87 GPR-23 silenced cells). Furthermore, in [³⁵S] GTPgS binding assay experiments, U87 GPR23 overexpressing cells showed an higher receptor activation in response to guanosine, as compared to U87 wt cells (EC₅₀= 8,067 nM in U87 GPR23-overexpressing cells and EC₅₀= 51nM in U87 wt cells). The binding site for [³H]-guanosine was highly specific and both lysophosphatidic acid (LPA) and guanine agonists were 10 times less effective than guanosine in displacing 50 nM [³H]-guanosine binding. All together these data suggest that GPR23 may act as a functional membrane receptor for guanosine.