CaMKII activity plays a role in μ-opioid receptor desensitization,251 which may be important for the development of opioid tolerance. CaMKII phosphorylates the μ-opioid receptor on Ser-261 and Ser-266 in the third intracellular loop, and phosphorylation at these sites mediates receptor desensitization, since mutation of these phosphorylation sites results in a receptor that does not show desensitization to repeated agonist administration.252
