An integrated view on the role of receptor mosaics at perisynaptic level: focus on adenosine A_2A, dopamine D₂, cannabinoid CB₁, and metabotropic glutamate mGlu₅ receptors

Abstract

The available evidence for receptor–receptor interactions between adenosine A_2A, dopamine D₂, cannabinoid CB₁, and metabotropic glutamate mGlu₅ receptors (A_2A, 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 A_2A 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.

Keywords::

• Receptor–receptor interactions
• receptor mosaics
• hub receptor
• receptor biochemical similarity
• horizontal molecular networks
• bioinformatics