GPCRs as Therapeutic Targets: a View on Adenosine Receptors Structure and Functions, and Molecular Modeling Support

D. Dal Ben, C. Lambertucci, S. Vittori, R. Volpini and G. Cristalli*

Dipartimento di Scienze Chimiche,Via S. Agostino, 1; Università di Camerino, 62032 Camerino, Italy

G-protein-coupled receptors (GPCRs) represent the largest known family of signal-transducing proteins and transmit signals for light and many extracellular regulatory molecules. GPCRs are dysfunctional or dysregulated in several human diseases and are estimated to be the targets of ~40% of the drugs used in clinical medicine today. Receptors for adenosine belong to this family, and so far four subtypes, the A₁, A_2A, A_2B, and A₃, have been recognized. The activation of adenosine receptors (ARs) is largely responsible for the variety of effects produced by adenosine throughout several organ systems. Based on the wide (and often beneficial) effects attributed to the accumulation of endogenously released adenosine,it has long been considered that regulation of ARs has considerable therapeutic potential. In this review, we focus on recent work on adenosine receptors as therapeutic targets and, in particular, on molecular modelling support to adenosine receptors targeting.

Keywords: G-protein-coupled receptors, Signal transduction, Adenosine, Adenosine receptors, Homology modeling