Preferential Coupling of Dopamine D 2S and D 2L Receptor Isoforms with G i1 and G i2 Proteins-In Silico Study.

The dopamine D ₂ receptor belongs to rhodopsin-like G protein-coupled receptors (GPCRs) and it is an important molecular target for the treatment of many disorders, including schizophrenia and Parkinson's disease. Here, computational methods were used to construct the full models of the dopamine D ₂ receptor short (D _2S ) and long (D _2L ) isoforms (differing with 29 amino acids insertion in the third intracellular loop, ICL3) and to study their coupling with G _i1 and G _i2 proteins. It was found that the D _2L isoform preferentially couples with the G _i2 protein and D _2S isoform with the G _i1 protein, which is in accordance with experimental data. Our findings give mechanistic insight into the interplay between isoforms of dopamine D ₂ receptors and G _i proteins subtypes, which is important to understand signaling by these receptors and their mediation by pharmaceuticals, in particular psychotic and antipsychotic agents.
Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.