text: Receptor uncoupling/phosphorylation is the most rapid form of desensitization that happens within a cell, as its effects are seen within seconds to minutes of agonist application. The ß adrenergic receptor was the first to have its desensitization studied and characterized. The mechanism of desensitization involves the action of a specific GRK, denoted ßARK, and also ß-arrestins. The ß-arrestins show high affinity for receptors that are both phosphorylated and activated, but are still able to bind non-phosphorylated receptors with a lower affinity. Additionally, ß-arrestins are better at inactivating ßARK-phosphorylated receptors rather than protein kinase A-phosphorylated receptors, which suggests that the arrestins preferentially mediate homologous desensitization.
  The mechanism of homologous desensitization for the β receptor is as follows:
  # Agonist binds and activates the receptor, which changes to an active conformational state.
  # Beta adrenergic receptor kinase (βARK), a cytoplasmic kinase is activated and phosphorylates the C-terminus of the β receptor.
  # This 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.