How can desensitization occur at receptors?

• A. Prolonged agonist exposure can cause receptor phosphorylation, internalization, and reduced responsiveness.
• B. Receptors become more responsive with repeated exposure.
• C. Desensitization occurs only with antagonist exposure.
• D. Receptor density increases upon desensitization.

Answer: (A)

When a receptor is continuously stimulated by an agonist, it can become less responsive overall. This happens because the active receptor gets modified by enzymes that add phosphate groups (receptor kinases). Phosphorylation promotes binding of beta-arrestin, which uncouples the receptor from its signaling partner and often leads to the receptor being pulled into the cell (internalized). With fewer receptors available on the surface and less signaling from each receptor, the cell’s response to the same drug diminishes. Sometimes this process also reduces the total number of receptors (downregulation), reinforcing the reduced responsiveness.

That’s why prolonged exposure to an agonist produces desensitization. The idea that receptors would become more responsive with repeated exposure describes sensitization, not desensitization. Desensitization is not limited to antagonist exposure, and increasing receptor density would be upregulation, not desensitization.