Homologous desensitization

Homologous desensitization occurs when a receptor decreases its response to an agonist at high concentration.

[3][4] Homologous desensitization serves as a mechanism for tachyphylaxis and helps organisms to maintain homeostasis.

The degradation and downregulation of receptors is often also associated with drug tolerance since it has a longer onset, from hours to days.

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 mechanism of desensitization involves the action of a specific GRK, denoted ßARK, and also ß-arrestins.

For example, different glycosylations on the exterior N-terminus of dopamine receptors D2 and D3 were associated with specific endocytotic pathways.