title: Several delta-opioid receptor ligands display no subtype selectivity to the human delta-opioid receptor.
abstract: Pharmacological studies performed in vivo suggested that the delta-opioid receptor could exist as two distinct subtypes, delta(1) and delta(2), while in vitro studies are inconclusive. Therefore, we measured the binding and functional selectivity of several putative delta(1)- and delta(2)-opioid receptor-selective compounds in membranes from Chinese hamster ovary cells stably expressing the human delta-opioid receptor. The compounds characterized were the agonists [D-Pen(2),D-Pen(5)]enkephalin (DPDPE, delta(1)) and deltorphin II (delta(2)), and the antagonists 7-benzylidenenaltrexone (BNTX, delta(1)), naltriben (delta(2)), naltrindole 5'-isothiocyanate (delta(2)), and naltrindole (delta(1) and delta(2)). In competition binding assays, all compounds tested showed no preference for the [3H]DPDPE, [3H]deltorphin II, or [3H]naltrindole binding sites. BNTX also showed no selectivity for the delta-opioid receptor over the mu-opioid receptor. In functional assays, the stimulation of [35S]GTPgammaS binding induced by either DPDPE or deltorphin II was potently inhibited by both delta(1)- and delta(2)-opioid receptor-selective antagonists. Together, these results indicate that these compounds are not selective for either the delta(1)- or delta(2)-opioid receptor binding sites in binding or functional assays.
authors.affiliation: Department of Pharmacology and Physiology, School of Medicine and Dentistry, The University of Rochester, PO Box 711, 601 Elmwood Avenue, Rochester, NY 14642-8711, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Parkhill
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
mesh_terms: D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004347:Drug Interactions; D006801:Humans; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection
chemical_list: D017465:Receptors, Opioid, delta