Ligand-induced Receptor Desensitization
Repeated or continuous administration of an agonist or an antagonist may lead to changes in the responsiveness of the receptor. To prevent potential damage to the cell (for example, high concentrations of calcium, initiating cell death), several mechanisms have evolved to protect a cell from excessive stimulation.
Tachyphylaxis
When repeated administration of a drug results in a diminished effect, the phenomenon is called tachyphylaxis. The receptor becomes desensitized to the action of the drug . In this phenomenon, the receptors are still present on the cell surface but are unresponsive to the ligand.
Endocytic Receptor Down Regulation
Other types of desensitization occur when receptors are down-regulated. Binding of the agonist results in molecular changes in the membrane-bound receptors, such that the receptor undergoes endocytosis and is sequestered from further agonist interaction. These receptors may be recycled to the cell surface, restoring sensitivity, or alternatively, may be further processed and degraded, decreasing the total number of receptors available.
Some receptors, particularly voltage-gated channels, require a finite time (rest period) following stimulation before they can be activated again. During this recovery phase they are said to be “refractory” or “unresponsive.”