Down-regulation is an adaptation of the cell to a situation of overstimulation and subsequent too large effect in the cell. The upper part of the graphic shows 3 consecutive steps of down-regulation.

  1. The physiological process usually describes a normal situation with 'normal' amounts of ligands and receptors.
  2. Then, (for example) when an agonist is added to a normal situation for a prolonged period of time, the cell becomes over-stimulated by the agonist.
  3. By decreasing the expression of the receptor the cell protects itself against continuous stimulation.

The lower part shows the different mechanisms by which the down-regulation can be performed. Signal transduction from activated receptors and signals from a high rate of internalisation result in decreased gene expression and corresponding receptor synthesis. Also more receptors are degraded and less receptors are recycled back to the membrane.

An example: receptor down-regulation occurs in diabetes type II patients using insulin.


Desensitization during prolonged treatment may occur with a number of drugs, eg with benzodiazepines or some anti-epileptics. Which mechanisms may lead to a reduced sensitivity of a receptor after long-term ligand exposure?