Upregulation
An increase in the number or sensitivity of receptors on a cell surface, typically occurring in response to reduced stimulation or prolonged antagonist exposure. Upregulation can lead to rebound effects when a drug is discontinued, as the increased receptor population becomes available to natural ligands.
Technical Context
Upregulation involves increased receptor gene transcription, enhanced mRNA stability, increased receptor protein synthesis, and/or decreased receptor internalisation and degradation. Clinically, upregulation creates the risk of supersensitivity when a chronically administered antagonist is discontinued — the upregulated receptors become suddenly available to endogenous agonists, potentially producing an exaggerated response (rebound phenomenon). For peptide drugs, understanding upregulation dynamics is important for managing drug discontinuation, dose tapering strategies, and predicting rebound effects.