Regulation of response

Regulation of response

Cells in the body are continuously bombarded by all kinds of ligands evoking stimulatory and inhibitory responses. A cell is able to integrate all these signals into one response. In the graphic only one receptor type is shown. Second messengers from the signal transduction, and ion concentrations play key roles in a coordinated cellular effect.

In response to the intensity of a certain signal, cells can increase (upregulate) or decrease (downregulate) the sensitivity to that signal. One way to achieve this is to change the number of receptors to a given hormone or neurotransmitter to alter its sensitivity to this molecule. This is a locally acting feedback mechanism.

When a ligand binds to its receptors on the surface of a cell, the effect will be started by signal transduction. This can e.g. lead to alterations in gene expression of all kinds of genes (including the receptor). Furthermore, internalisation provides a way to regulate the number of sites that are available for binding on the cell’s surface. At high ligand concentrations, the number of surface receptors is gradually reduced by the accelerated rate of receptor internalisation and degradation. The rate of synthesis of new receptors within the cell and their insertion in the plasma membrane normally keep pace with their rate of destruction.


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?