TRC: Down-regulation

Down-regulation

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may cause some types of receptors to dissociate from post-receptor processes, to ‘fall apart’ in subunits, to be ‘withdrawn’ from the cell surface and/or to be recycled less rapidly.

Option explanation:

Decrease in receptor degradation and increase in receptor recycling

Decrease in receptor sensitivity and increase in receptor expression

Increase in receptor degradation and decrease in receptor recycling

Increase in receptor sensitivity and decrease in receptor expression

Down-regulation

Down-regulation

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