Morphiceptin: biphasic inhibition of mu-opiate receptor ligands

The interaction between morphiceptin and the morphine (mu) opiate receptor present in rat brain membranes has been examined. Detailed competitive displacement curves of morphiceptin against the mu receptor ligands [3H]fentanyl and [3H]naloxone were biphasic, with Hill coefficients of 0.78 and 0.60 respectively. Hoftsee plots of these displacement curves suggested that 30-35% of the morphiceptin binding was to a high affinity site and the residual binding was to a site with lower affinity. These results indicate that morphiceptin binding to the mu opiate receptor does not obey the law of mass action, and raises the possibility that morphiceptin distinguishes subclasses of mu binding site.