In heterologous desensitization, activating receptor A desensizes which receptor?

• A. Only receptor A
• B. Only receptor B
• C. Receptor C
• D. Receptor B (desensitized by activation of A)

Answer: (D)

In heterologous desensitization, triggering one receptor can dampen the response of a different receptor through shared signaling pathways. When receptor A is activated, kinases such as GRKs and second-messenger kinases like PKA or PKC get activated and can phosphorylate receptor B even though B wasn’t activated. This phosphorylation promotes arrestin binding, uncouples B from its G proteins, and often leads to internalization, all of which reduce B’s signaling. So the receptor that becomes desensitized is receptor B as a consequence of activating receptor A. The other possibilities would involve the first receptor being desensitized itself, which isn’t the case here.