desensitization
Desensitization is the body turning down its own sensitivity to a signal that keeps shouting. After a receptor is stimulated hard or for a long time, it stops responding as strongly — like ears that tune out a constant loud noise.
Several cellular mechanisms produce this. With many G-protein-coupled receptors, sustained agonist exposure leads to the receptor being phosphorylated and bound by beta-arrestin, which uncouples it from its signalling pathway and triggers its internalisation away from the cell surface. Over longer periods the cell may also reduce the total number of receptors (down-regulation). The result is a weaker effect from the same dose of drug.
Desensitization is a major reason drug effects can fade with continued use, contributing to tolerance. It can be homologous (specific to the over-stimulated receptor) or heterologous (spreading to other receptors via shared downstream components). Clinically it explains why some drugs lose effect over days to weeks, and why drug holidays or dose adjustments are sometimes needed.
Continuous use of an inhaled beta-2 agonist can desensitize and down-regulate airway beta-2 receptors, blunting the bronchodilator response over time.
A fading response to repeated stimulation.
Desensitization is usually slower and longer-lasting than tachyphylaxis; the latter often refers to a rapid drop in response over just minutes to hours of closely spaced dosing.