Homologous desensitization

Homologous desensitization occurs when a receptor decreases its response to a signalling molecule when that agonist is in high concentration.[1] It 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.[2]

Homologous desensitization should not be confused with heterologous desensitisation, which is a different process whereby repeated stimulation of a receptor by one agonist results in desensitivity to a range of other agonists.

Mechanism

The mechanism 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.

References

  1. ^ "homologous desensitization". Medical Dictionary. Drugs.com. http://www.drugs.com/dict/homologous-desensitization.html. Retrieved 18 May 2011. 
  2. ^ Fehmann, HC; Habener, JF (1991 Jun). "Homologous desensitization of the insulinotropic glucagon-like peptide-I (7-37) receptor on insulinoma (HIT-T15) cells.". Endocrinology 128 (6): 2880–8. doi:10.1210/endo-128-6-2880. PMID 1645253.