What is desensitization in pharmacology?

• A. A mechanism that in the prolonged presence of an agonist, the receptor becomes desensitized/inactivated
• B. An increase in receptor sensitivity
• C. A permanent receptor loss
• D. The process of receptor synthesis

Answer: (A)

Desensitization is when a receptor loses its responsiveness after repeated or prolonged exposure to an agonist. The cell has a built-in way to dampen signaling to prevent overstimulation: the receptor gets modified and its ability to couple to its G protein is reduced or the receptor is removed from the surface. This makes the usual signal weaker even though the drug is still present.

The best description reflects this mechanism: continuing presence of an agonist leads the receptor to become desensitized or inactivated. Mechanistically, this often involves receptor phosphorylation, recruitment of proteins like β-arrestin, and internalization of the receptor, which decreases signaling from that receptor pool. If the agonist is removed, signaling can recover over time as receptors are resensitized or recycled.

Why the other ideas don’t fit as well: increasing receptor sensitivity describes sensitization, the opposite of desensitization. Permanent receptor loss implies irreversible loss beyond the usual reversible desensitization, which is not the standard definition. Receptor synthesis refers to making new receptors, not reducing responsiveness.