Homologous desensitization

Desensitization of receptors is a process whereby after prolonged agonist exposure, the receptor is uncoupled from its signaling cascade, and thus the biological effect of receptor activation is attenuated. High ligand concentrations are required to produce homologous desensitization. Homologous desensitization should not be confused with heterologous desensitisation, which has some similarities, but is a different process.

The process of homologous desensitization is as follows (using the β₂ receptor as an example):

1. Agonist binds and activates receptor which changes to an active conformational state.
2. Beta adrenergic receptor kinase (BARK), a cytoplasmic kinase is activated and phosphorylates the C-terminus of the β₂ receptor.
3. Such phosphorylation increases the affinity of β-arrestin for the receptor, resulting in uncoupling of the α subunit of the heterotrimeric G-protein from the receptor producing desensitization.