Evidence for the existence of a specific G protein-coupled receptor activated by guanosine

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.