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.
- The physiological process usually describes a normal situation with 'normal' amounts of ligands and receptors.
- 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.
- 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?
Extra info: Strong ligand binding or prolonged stimulation of receptors may cause some types of receptors to dissociate from post-receptor processes, to ‘fall apart’ in subunits, to be ‘withdrawn’ from the cell surface and/or to be recycled less rapidly.