Brain expression and 3H-Guanosine binding analysis of novel G protein-coupled receptor for guanosine (GPR23/LPA4)

Several studies have shown that guanine-based purines exert biological effects on the central nervous system, possibly through membrane receptor. In a parallel work, we have identified the first guanosine G protein-coupled receptor GPR23, known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell lines. Here, we performed in different brain areas the following studies: by PCR, the expression levels of GPR23; by [3H]-Guanosine radioligand binding assay, the binding properties of GPR23; by [35S] GTPγS binding assay, the receptor activation properties of guanosine. Among the examined areas, the cerebral cortex showed the highest GPR2…

Identification of GPR23/LPA4 as a candidate G protein-coupled receptor for Guanosine

Identification and functional binding analysis of GPR23/! LPA4 as a candidate G protein-coupled receptor for Guanosine.

Several studies have shown that guanine-based purines exert biological effects on the central nervous system (CNS), possibly through membrane receptors, but at the present there are not reports related to the identification of such specific receptor(s). We have identified the first guanosine G protein-coupled receptor GPR23, also known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell line (U87). We report that the silencing of GPR23 reduces significantly the antiproliferative effects of guanosine, while stably transfected cell clones over-expressing GPR23 increase sensitivity to guanosine. [3H] Guanosine radioligand binding as…

Climate change fosters the decline of epiphytic Lobaria species in Italy

Similarly to other Mediterranean regions, Italy is expected to experience dramatic climatic changes in the coming decades. Do to their poikilohydric nature, lichens are among the most sensitive organisms to climate change and species requiring temperate-humid conditions may rapidly decline in Italy, such in the case of the epiphytic Lobaria species that are confined to humid forests. Our study, based on ecological niche modelling of occurrence data of three Lobaria species, revealed that in the next decades climate change will impact their distribution range across Italy, predicting a steep gradient of increasing range loss across time slices. Lobaria species are therefore facing a high ext…

Guanosine-Mediated Anxiolytic-Like Effect: Interplay with Adenosine A1 and A2A Receptors

Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, …

IDENTIFICATION AND FUNCTIONAL CHARACTERIZATION OF GPCR23/LPA4 AS A CANDIDATE G PROTEIN-COUPLED RECEPTOR FOR GUANOSINE

La guanosina esercita diverse funzioni a livello del Sistema Nervoso Centrale, coinvolgendo recettori di membrana accoppiati a proteine G (GPCR) non ancora identificati. Pertanto, l’obiettivo della ricerca è stato quello di individuare e caratterizzare uno specifico recettore funzionale per la Guanosina. I dati ottenuti su linee cellulari hanno dimostrato che il legame della guanosina con le membrane plasmatiche è incrementato dall’over-espressione del GPCR23 e ridotto dal suo silenziamento ed hanno evidenziato l’attivazione di un GPCR in risposta alla guanosina. A livello cerebrale il GPCR23 è risultato essere maggiormente espresso nella regione corticale, dove si è dimostrata anche una no…