PHARMACOLOGICAL STUDY OF DIHYDROETORPHINE IN CLONED MU-OPIOID, DELTA-OPIOID AND KAPPA-OPIOID RECEPTORS

We investigated the binding characteristics of dihydroetorphine, 7,8-d ihydro-7 methylbutyl]-6,14-endoethano-tetrahydro-oripavine, and its ef fect on the inhibitory system of cyclic AMP production using cloned mu -, delta- and kappa-opioid receptors expressed on Chinese hamster ovar y cells. The K-i values of dihydroetorphine for the mu-, delta- and ka ppa-opioid receptors were 4.5 x 10(-10) 1.8 x 10(-9) and 5.7 x 10(-10) M, respectively. On the other hand, those of morphine were 1.9 x 10(- 9), 1.4 x 10(-6) and 1.3 x 10(-7) M, respectively. Through all of thes e three types of opioid receptors, dihydroetorphine inhibited forskoli n (10 mu M)-stimulated cyclic AMP production via pertussis toxin-sensi tive G protein(s), and the inhibitory effects were antagonized by co-a pplication with opioid receptor antagonists. The IC50 values of dihydr oetorphine for the inhibition of cyclic AMP production through the mu- , delta- and kappa-opioid receptors were 4.2 x 10(-11), 8.6 x 10(-10) and 4.3 x 10(-9) M, respectively. On the other hand, those of morphine were 2.6 x 10(-8), 2.6 x 10(-6) and 1.9 x 10(-6) M, respectively. The se results indicate that dihydroetorphine, unlike morphine which prefe rentially binds the mu-opioid receptor, binds not only mu- but also de lta- and kappa-opioid receptors with high affinity and acts as a more potent agonist than morphine for all of the three types of receptors.