Pharmacological and genetic manipulations at the µ-opioid receptor reveal arrestin-3 engagement limits analgesic tolerance and does not exacerbate respiratory depression in mice.

ABSTRACT: Opioid drugs are widely used analgesics that activate the G protein-coupled µ-opioid receptor, whose endogenous neuropeptide agonists, endorphins and enkephalins, are potent pain relievers. The therapeutic utility of opioid drugs is hindered by development of tolerance to the analgesic effects, requiring dose escalation for persistent pain control and leading to overdose and fatal respiratory distress. The prevailing hypothesis is that the intended analgesic effects of opioid drugs are mediated by µ-opioid receptor signaling to G protein, while the side-effects of respiratory depression and analgesic tolerance are caused by engagement of the receptor with the arrestin-3 protein. Consequently, opioid drug development has focused exclusively on identifying agonists devoid of arrestin-3 engag

SUBMITTER: He L 

PROVIDER: S-EPMC8581001 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature