enkephalin--ala(2)-mephe(4)-gly(5)- and oripavine

This study examines the possibility that oripavine opioid receptor agonists bind equally to both high and low affinity states of the mu-opioid receptor. Studies were performed in C6 cells expressing mu- or delta-opioid receptors; high and low agonist affinity states of the receptors were defined by the absence and presence, respectively of Na+ ions and the GTP analog Gpp(NH)p. At the mu-opioid receptor dihydroetorphine and etorphine were full agonists, buprenorphine had moderate efficacy while diprenorphine was an antagonist. At the delta-opioid receptor, dihydroetorphine, etorphine, and diprenorphine had moderate efficacy while buprenorphine was an antagonist. The binding affinities of the oripavines at the mu-opioid receptor decreased only one to 2-fold in the presence of NaCl and Gpp(NH)p. In contrast, decreases in oripavine affinity at the delta-opioid receptor correlated with delta-opioid receptor efficacy. The ability of oripavine agonists to bind with high affinity to the low agonist affinity state of the nu-opioid receptor may explain the high potencies of these compounds in vivo.

Topics: Analgesics, Opioid; Animals; Benzamides; Binding, Competitive; Buprenorphine; Cloning, Molecular; Diprenorphine; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Etorphine; Fentanyl; Guanosine 5'-O-(3-Thiotriphosphate); Morphine; Naloxone; Piperazines; Radioligand Assay; Rats; Receptors, Opioid, delta; Receptors, Opioid, mu; Sulfur Radioisotopes; Thebaine; Tritium; Tumor Cells, Cultured