title: Differential binding properties of oripavines at cloned mu- and delta-opioid receptors.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Michigan, Ann Arbor 48109-0632, USA.
authors.forename: K O
authors.initials: KO
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Akil
authors.forename: J H
authors.initials: JH
authors.lastname: Woods
authors.forename: J R
authors.initials: JR
authors.lastname: Traynor
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology; D003001:Cloning, Molecular; D004174:Diprenorphine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005048:Etorphine / Q000031:analogs & derivatives / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013797:Thebaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D000701:Analgesics, Opioid; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D004174:Diprenorphine; D013797:Thebaine; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002047:Buprenorphine; D005048:Etorphine; C005283:oripavine; D009020:Morphine; C034765:18,19-dihydroetorphine; D005283:Fentanyl