DEFINITION
Receptor desensitisation is the diminished responsiveness of a receptor during sustained or repeated agonist exposure. For GPCRs, it is typically initiated by GRK-mediated phosphorylation of the activated receptor, followed by β-arrestin binding, uncoupling from G-proteins and internalisation.
Different agonists at the same receptor can drive desensitisation to different degrees — a property closely linked to biased agonism.
WHY IT MATTERS
Desensitisation is the receptor-level counterpart to observed tachyphylaxis and shapes chronic dosing behaviour.
RELATED
Compounds