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7. Response to Excessive and Reduced Stimulation of Receptors:

Excessive Receptor Activation can result in desensitization or down regulation.

Desensitization: receptor becomes less responsive when exposed to a high concentration of an agonist drug for a long duration (several minutes).

What is an example of receptor desensitization?

Under normal physiological conditions acetylcholine stimulates nicotinic acetylcholine receptors on skeletal muscle to open an ion channel that allows calcium influx to cause muscle contraction. Acetylcholine is hydrolyzed rapidly by acetylcholinesterase; the channel closes and is ready to be opened again upon the arrival of new acetylcholine molecules. Pharmacological inhibitors of acetylcholine esterase cause accumulation of high concentrations of acetylcholine in the synaptic cleft. The ion channel on the receptor becomes insensitive to acetylcholine in attempt to protect the muscle from being overly activated.

Down Regulation: the number of receptors decreases (by proteolysis) upon exposure to a high concentration of agonist for a very long time (hours), making the cell less responsive to the same agonist or others that work at the same receptor.

What is an example of downregulation?

Type 2 Diabetes: chronic increased levels of glucose leads to increased production of insulin. Over time, insulin receptors downregulate making the individual less sensitive to insulin.

Reduced Receptor stimulation: can result in receptor supersensitivity and upregulation.

Supersensitivity and Upregulation: occurs when a cell is deprived of its natural ligand for a long time, resulting in increased receptor expression over time and making the cell more sensitive to its ligand

What is an example of supersensitivity?

Reserpine depletes stores of catecholamines (e.g. norepinephrine) in neurons. Catecholamine receptors compensate by becoming more abundant and therefore more responsive to exogenous catecholamine-like drugs.


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Principles of Pharmacology - Study Guide Copyright © by Edited by Dr. Esam El-Fakahany and Becky Merkey, MEd is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.