On the Role of the Balance of GPCR Homo/ Heteroreceptor Complexes in the Brain

The early work on neuropeptide-monoamine receptor-receptor interactions in the Central Nervous System the first indications of the existence of G protein-coupled receptors (GPCRs) heteroreceptor complexes and the field began to expand from monomers into heteromers and higher order heteromers, including also GPCR-ion , Receptor Tyrosine Kinases (RTK)-GPCR and Receptor activity-modifying proteins-GPCR heteroreceptor . The existence of heteroreceptor complexes with allosteric receptor-receptor interactions increases the of receptor function including recognition, trafficking and signalling. We have proposed the molecular of receptor-receptor interactions as a good way to understand of how brain function can increase through integration of signals. An alteration in specific receptor-receptor interactions or their balance/equilibrium (with corresponding monomers-homomers) are indeed considered to have a role in the pathogenic mechanisms that lead various diseases, including drug addiction, depression, Parkinson's disease and schizophrenia. Therefore, targeting -protomer interactions in heteroreceptor complexes or the balance with their corresponding homoreceptor in discrete brain regions may become an important field for developing novel drugs, including heterobivalent and optimal types of combined treatments. Increasing our understanding of molecular integration of signals via receptor-receptor interactions in the heteroreceptor complexes will have a major impact on the molecular , leading to novel strategies for drug discovery and treatment of diseases.