title: Biochemical evidence for orphanin FQ/nociceptin receptor heterogeneity in mouse brain.
abstract: A recently identified novel peptide, orphanin FQ/nociceptin (OFQ/N), is an endogenous ligand for a unique member of the cloned opioid receptor family. Saturation studies in mouse brain membranes reveal curvilinear Scatchard plots with both a higher (KD 3.8 pM, Bmax 31.6 fmol/mg protein) and a lower (KD 896 pM, Bmax 233 fmol/mg protein) affinity site in brain tissue, compared to only a single site in transfected CHO cells (KD 36 pM). Competition studies confirm the high affinity of OFQ/N for this site, but shallow Hill slopes suggest heterogeneity. Traditional opioids have poor affinity for this receptor and OFQ/N and its fragments do not label traditional opioid receptors. In brain homogenates, both OFQ/N and OFQ/N(1-11) inhibit forskolin-stimulated camp accumulation with IC50 values of 1 nM or less, an action which is readily reversed by opioid antagonists. OFQ/N(1-7) shows little activity. Together, these studies suggest the presence of heterogeneous, functionally active OFQ/N receptors in mouse brain.
authors.affiliation: The George C. Cotzias Laboratory of Neuro-Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Mathis
authors.forename: J
authors.initials: J
authors.lastname: Ryan-Moro
authors.forename: A
authors.initials: A
authors.lastname: Chang
authors.forename: J S
authors.initials: JS
authors.lastname: Hom
authors.forename: D A
authors.initials: DA
authors.lastname: Scheinberg
authors.forename: G W
authors.initials: GW
authors.lastname: Pasternak
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D004399:Dynorphins / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009294:Narcotics / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D004399:Dynorphins; D004745:Enkephalins; D009294:Narcotics; D018847:Opioid Peptides; D011957:Receptors, Opioid; D011994:Recombinant Proteins; D000094942:Nociceptin Receptor; D000097629:Nociceptin