%0 Journal Article %A Michael S. Virk %A John T. Williams %T Agonist-Specific Regulation of μ-Opioid Receptor Desensitization and Recovery from Desensitization %D 2008 %R 10.1124/mol.107.042952 %J Molecular Pharmacology %P 1301-1308 %V 73 %N 4 %X Agonist-selective actions of opioids on the desensitization of μ-opioid receptors (MORs) have been well characterized, but few if any studies have examined agonist-dependent recovery from desensitization. The outward potassium current induced by several opioids was studied using whole-cell voltage-clamp recordings in locus ceruleus neurons. A brief application of the irreversible opioid antagonist β-chlornaltrexamine (β-CNA) was applied immediately after treatment of slices with saturating concentrations of opioid agonists. This approach permitted the measurement of desensitization and recovery from desensitization using multiple opioid agonists, including [Met]5enkephalin (ME), [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO), etorphine, fentanyl, methadone, morphine, morphine-6-glucuronide, oxycodone, and oxymorphone. The results indicate that desensitization protects receptors from irreversible antagonism with β-CNA. The amount of desensitization was measured as the decrease in current during a 10-min application of a saturating agonist concentration and was a good predictor of the extent of receptor protection from irreversible inactivation with β-CNA. After desensitization with ME or DAMGO and treatment with β-CNA, there was an initial profound inhibition of MOR-induced current that recovered significantly after 45 min. There was, however, no recovery of MOR-mediated current with time after treatment with agonists that did not cause desensitization, such as oxycodone. These results demonstrate that desensitization prevents irreversible inactivation of receptors by β-CNA. The American Society for Pharmacology and Experimental Therapeutics %U https://molpharm.aspetjournals.org/content/molpharm/73/4/1301.full.pdf