Steps involved in the homologous desensitization of GPCRs. According to the classical model of homologous desensitization, receptor activation by an agonist induces a series of conformational changes that trigger receptor signalling and regulation. The first of these regulatory steps is receptor phosphorylation by GRK (1). Once phosphorylated receptor affinity for βarrestin increases, enhancing interaction between the two proteins (2) and promoting internalization (3). Internalized receptors are then directed to early/sorting endodomes where interaction with different regulatory proteins will allow them to recycle back to the membrane (4) or will directed towards degradation (5).