Tolerance to Opioid Drugs is Linked to the Cell Membrane Cholesterol Gene and a Key GPCR

PTCHD1, a protein that is involved in altering cholesterol content in a cells membrane, is involved in controlling opioid responses by regulating -opioid receptor (MOR) trafficking.

The researchers claim that their discovery opens the door to other treatments, as well as new directions for pain medications that reduce the likelihood of tolerance.

Martemyanov, a senior author, and co-authors, including former Scripps Research staffers Brock Grill, PhD, who is now working at the University of Washington Medical School, published their findings in Nature Neuroscience.

In a paper titled, Ptchd1 mediates opioid tolerance via cholesterol-dependent effects on -opioid receptor trafficking, they concluded. we propose that Ptchd1 plays an evolutionarily conserved role in protecting the -opioid receptor against over

Martemyanov claims that over time, the most effective prescription pain relievers lose their effectiveness. To satisfy patients with the same pain-relieving effect, doctors often prescribe higher and higher dosages.

GPCRs are highly beneficial to scientists because they enable medications and biological molecules to enter the cells' surface. 

However, the molecular and cellular mechanisms underlying several key GPCR properties are still poorly understood. One such dark area is tolerance, a behavioral phenomenon resulting from the cellular process of GPCR desensitization.