It is known that, unlike most opiates (i.e. fentanyl, etorphine, DAMGO and β-endorphin), morphine exhibits a unique pharmacological profile with a propensity to promote slower and incomplete receptor internalization with a typical exposure time greater than 5 min30. In our electrophysiological experiments, exposure of the cells to morphine was generally less than 40 seconds (see Figure 3A and Figure 3C). Hence, the observed difference is not likely a result of significant altered receptor internalization rates. Nevertheless, our data suggest that the physiological response of the opioid receptor variants is ligand-dependent and that morphine’s ‘recognition’ of the mutant receptor diminishes its analgesic effectiveness.
