G-Protein Coupled Receptors

Receptor de-sensitization is a phenomenon peculiar to G-protein coupled receptors, by which the receptor becomes un-responsive to agonist challenges in the continued presence of the agonist.

Receptor De-Sensitization - Inactive State

Prolonged stimulation of G-protein coupled receptors is believed to result in phosphorylation of serine and threonine residues associated with the 3_rd cytoplasmic loop of the receptor.

Phosphorylation results in a conformational change in the receptor, effectively returning it to the inactive conformation, which is incapable of activating the G-protein.

Although the exact mechanism of desensitization remains obscure, a protein known as beta-arrestin is believed to be involved in the desensitization process. This protein selectively binds the phosphorylated cytoplasmic loop of the receptor and is thought to be responsible for inducing the conformational change back to the inactive form of the receptor.