title: Extraordinary potency of a novel delta opioid receptor agonist is due in part to increased efficacy.
abstract: A new cyclic opioid peptide of sequence Tyr-D-Pen-Gly-Phe-Cys-Phe (HBP2) was examined in the mouse isolated vas deferens (MVD) bioassay. Studies with receptor-selective opioid antagonists showed the peptide to be highly selective for delta opioid receptors. HBP2 and the standard delta agonist DPDPE were simultaneously compared using the technique of partial irreversible receptor blockade; data were analyzed using the operational model of pharmacologic agonism. HBP2 was approximately 160 times as potent as DPDPE; estimation of the affinity and efficacy of the two peptides revealed that the potency increase was due to a 5.3-fold increase in efficacy, as well as a 37-fold increase affinity. This contrasts with our previous findings with other cyclic enkephalin analogs, in which increased affinity was achieved without a change in apparent efficacy. Analysis of concentration-response curve shape suggested in addition the possibility of heterogeneity in transduction mechanisms for MVD delta receptors.
authors.affiliation: Department of Anesthesia, The University of Pennsylvania School of Medicine, Philadelphia 19104-4283, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Kramer
authors.forename: H
authors.initials: H
authors.lastname: Bartosz-Bechowski
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
authors.forename: F
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D014649:Vas Deferens / Q000187:drug effects
chemical_list: D004745:Enkephalins; D009292:Narcotic Antagonists; D010455:Peptides; D010456:Peptides, Cyclic; D017465:Receptors, Opioid, delta; C085404:tyrosyl-cyclo(penicillamyl-glycyl-phenylalanyl-cysteinyl)phenylalanine; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C009862:connective tissue-activating peptide; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole