Homologous desensitization

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

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

1. Agonist binds and activates receptor which changes to an active conformational state.

2. βARK, 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 desensitisation.

Compare to heterologous desensitisation.