Evidence for the Existence of a Specific G Protein-Coupled Receptor Activated by Guanosine

• Published in: ChemMedChem Vol. 6; no. 6; pp. 1074 - 1080
• Main Authors: Volpini, Rosaria, Marucci, Gabriella, Buccioni, Michela, Dal Ben, Diego, Lambertucci, Catia, Lammi, Carmen, Mishra, Ram C., Thomas, Ajiroghene, Cristalli, Gloria
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 06.06.2011; WILEY‐VCH Verlag
• Subjects: Animals; Binding Sites; Brain - metabolism; Cell Membrane - metabolism; Eu-GTP; GPCR; guanosine; Guanosine - analogs & derivatives; Guanosine - metabolism; Guanosine Triphosphate - metabolism; nucleosides; Protein Binding; Rats; receptors; Receptors, G-Protein-Coupled - metabolism
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201100100

Guanosine, released extracellularly from neurons and glial cells, plays important roles in the central nervous system, including neuroprotection. The innovative DELFIA Eu‐GTP binding assay was optimized for characterization of the putative guanosine receptor binding site at rat brain membranes by using a series of novel and known guanosine derivatives. These nucleosides were prepared by modifying the purine and sugar moieties of guanosine at the 6‐ and 5′‐positions, respectively. Results of these experiments prove that guanosine, 6‐thioguanosine, and their derivatives activate a G protein‐coupled receptor that is different from the well‐characterized adenosine receptors. Catching the elusive guanosine receptor: The innovative DELFIA Eu‐GTP binding assay was applied to characterize the guanosine binding site by using novel and known guanosine derivatives. Some of the tested compounds, which proved to be full agonists with EC50 values in the low nanomolar range, could be useful tools for further characterization of the putative guanosine receptor.