An integrated view on the role of receptor mosaics at perisynaptic level: focus on adenosine A(2A), dopamine D(2), cannabinoid CB(1), and metabotropic glutamate mGlu(5) receptors.

The available evidence for receptor–receptor interactions between adenosine A2A, dopamine D2, cannabinoid CB1, and metabotropic glutamate mGlu5 receptors (A2A, D2, CB1, and mGlu5, respectively) is revised under the “receptor mosaic” perspective. Furthermore, the concept of “hub receptor” is defined in accordance with informatics and it is tentatively illustrated in the case of the hypothesized tetramer formed by the above mentioned receptors. On the basis of some biochemical features of the four receptors and of a bioinformatics analysis, an objective deduction of their “similarity” has been obtained. To this aim the Canberra, Euclidean and Chebyshev multivariate distance metrics have been used. It is interesting to note that A2A and D2 are the most different ones, while CB1 and mGlu5 are the most similar ones among the four receptors analyzed. Finally, by means of a bioinformatics analysis based on different approaches the possible binding sites mediating G-protein-coupled receptor (GPCR) interactions have been indicated. It is interesting to note that in some instances accordance has been found between the bioinformatics indications and the available experimental data.