Down-regulation
 (Science: physiology) development of a refractory or tolerant state consequent upon repeated administration of a pharmacologically or physiologically active substance.
 It is the process that decreases ligand and receptor interactions or reduces the responsiveness of a cell to a stimulus following first exposure.
 this is often accompanied by an initial decrease in affinity of receptors for the agent and a subsequent reduction in the number of available receptors expressed on the surface which can result from internalisation of the ligand:receptor complex or from decreased expression of the receptor.
 Classically the concept referred to hormone receptors but contemporary usage includes other cell surface receptors.
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