Which of the following is a mechanism of desensitization?

• A. Modification of receptor subunits
• B. Increased receptor numbers
• C. Enhanced ligand affinity
• D. Desensitization by receptor stimulation

Answer: (A)

Desensitization happens when the signaling by a receptor decreases despite ongoing presence of the activating ligand, and a common way this occurs is through modification of the receptor itself. When receptor subunits are chemically modified—most notably by phosphorylation by GPCR kinases or other kinases—the receptor changes shape or coupling properties, which weakens or prevents its ability to activate the associated G proteins. This can also promote arrestin binding and receptor uncoupling, and often leads to receptor internalization, all of which reduce the cell’s response to the same level of ligand.

Increasing receptor numbers would boost responsiveness rather than dampen it. Enhancing ligand affinity would make the receptor more sensitive, not desensitize it. Desensitization by receptor stimulation describes the phenomenon itself rather than a discrete mechanism, whereas modifying receptor subunits is a clear mechanistic route by which signaling is reduced.