Molecular integration via allosteric interactions in receptor heteromers. A working hypothesis

The intramembrane receptor–receptor interactions among GPCRs demonstrated in the beginning of the 80s in the CNS probably reflect the existence of allosteric mechanisms in receptor heteromers, and the postulated assemblies of multiple GPCRs coined ‘receptor mosaics’ in the early 80s probably represent higher order receptor heteromers, recently demonstrated with novel biophysical techniques in living cells. The receptor interface in the GPCR heteromers is beginning to be characterized and in adenosine A2A–dopamine D2-like heteromers the electrostatic arginine–phosphate salt bridge seems to be a hot spot in the interface with covalent-like stability, possibly participating in the allosteric interactions and making possible integration of heteromer receptor function. We discuss the possible relevance of some putative D2 receptor heteromers in the treatment of Parkinson's disease and schizophrenia, respectively.