Identification of a high‐affinity orphanin FQ/nociceptin(1–11) binding site in mouse brain
The presence of pairs of basic amino acids within the orphanin FQ/Nociceptin (OFQ/N) sequence has raised the possibility that truncated versions of the peptide might be physiologically important. OFQ/N(1–11) is pharmacologically active in mice, despite its poor affinity in binding assays (Ki > 250 nM) for the OFQ/N receptor. Using an analog of OFQ/N(1–11), [125I][Tyr10]OFQ/N(1–11), we identified a high‐affinity binding site (KD 234 pM; Bmax 43 fmol/mg protein) with a selectivity profile distinct from the OFQ/N receptor and all the traditional opioid receptors. This site had very high affinity for OFQ/N and its related peptides. The most striking differences between the new site and the OFQ/N receptor previously observed in brain were seen with traditional opioids. Dynorphin A analogs and α‐neoendorphin competed with [125I][Tyr10]OFQ/N(1–11) binding in mouse brain with Ki values below 10 nM, while naloxone benzoylhydrazone (Ki 3.9 nM) labeled the [125I][Tyr10]OFQ/N(1–11) binding site as potently as many traditional opioid receptors. Several other opioids, including fentanyl, (−)cyclazocine, levallorphan, naltrindole, and diprenorphine, also displayed moderate affinities for this site. Finally, the [125I][Tyr10]OFQ/N(1–11) site had a unique regional distribution consistent with a distinct receptor. Thus, [125I][Tyr10]OFQ/N(1–11) labels a novel site in brain with a selectivity profile intermediate between that of either opioid or OFQ/N receptors. Synapse 34:181–186, 1999. © 1999 Wiley‐Liss, Inc.
Number of times cited according to CrossRef: 16
- Bryony L. Winters, Macdonald J. Christie and Christopher W. Vaughan, Electrophysiological Actions of N/OFQ, , 10.1007/164_2019_205, (2019).
- Yan-Yu Liao, Cynthia Wei-Sheng Lee, Ing-Kang Ho and Lih-Chu Chiou, Quantitative study of [Tyr10]nociceptin/orphanin FQ (1-11) at NOP receptors in rat periaqueductal gray and expressed NOP receptors in HEK293 cells, Life Sciences, 90, 7-8, (306), (2012).
- Soh Katsuyama, Hirokazu Mizoguchi, Takaaki Komatsu, Chikai Sakurada, Minoru Tsuzuki, Shinobu Sakurada and Tsukasa Sakurada, Antinociceptive effects of spinally administered nociceptin/orphanin FQ and its N-terminal fragments on capsaicin-induced nociception, Peptides, 32, 7, (1530), (2011).
- Yan-Yu Liao, Faming Jiang and Lih-Chu Chiou, Quantitative study of the antagonistic effect of (−)-cis-1-Methyl-7-[[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl]-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ol (SB-612111) on nociceptin/orphanin FQ-mediated potassium channel activation in rat periaqueductal gray slices, European Journal of Pharmacology, 657, 1-3, (84), (2011).
- Yan-Yu Liao, Claudio Trapella and Lih-Chu Chiou, 1-Benzyl-N-[3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl]pyrrolidine-2-carboxamide (Compound 24) antagonizes NOP receptor-mediated potassium channel activation in rat periaqueductal gray slices, European Journal of Pharmacology, 606, 1-3, (84), (2009).
- Liliana Carmona-Aparicio, Fernando Peña, Anna Borsodi and Luisa Rocha, Effects of nociceptin on the spread and seizure activity in the rat amygdala kindling model: Their correlations with 3H-leucyl-nociceptin binding, Epilepsy Research, 77, 2-3, (75), (2007).
- Daniel Feller, xPharm: The Comprehensive Pharmacology Reference, (1), (2007).
- Tsukasa Sakurada, Takaaki Komatsu, Tomoko Moriyama, Mika Sasaki, Kengo Sanai, Tohru Orito, Chikai Sakurada and Shinobu Sakurada, Effects of intraplantar injections of nociceptin and its N-terminal fragments on nociceptive and desensitized responses induced by capsaicin in mice, Peptides, 26, 12, (2505), (2005).
- A Berthele, S Platzer, D Dworzak, J Schadrack, B Mahal, A Büttner, H.P Aßmus, K Wurster, W Zieglgänsberger, B Conrad and T.R Tölle, [3h]-nociceptin ligand-binding and nociceptin opioid receptor mrna expression in the human brain, Neuroscience, 121, 3, (629), (2003).
- Charles R. Neal, Huda Akil and Stanley J. Watson, Chapter III Neuroanatomical studies of the opioid receptor-like-1 receptor and its endogenous neuropeptide orphanin FQ (nociceptin), Peptide Receptors Part II, 10.1016/S0924-8196(02)80005-7, (103-193), (2002).
- Ying-Xian Pan, Elizabeth Bolan and Gavril W Pasternak, Dimerization of morphine and orphanin FQ/nociceptin receptors: generation of a novel opioid receptor subtype, Biochemical and Biophysical Research Communications, 297, 3, (659), (2002).
- Chikai Sakurada, Shinobu Sakurada, Tohru Orito, Koichi Tan-No and Tsukasa Sakurada, Degradation of nociceptin (orphanin FQ) by mouse spinal cord synaptic membranes is triggered by endopeptidase-24.11: an in vitro and in vivo study, Biochemical Pharmacology, 64, 8, (1293), (2002).
- Piotr Suder, David Wade, Anna Łęgowska, Jolanta Kotlińska, Krzysztof Rolka and Jerzy Silberring, Dynorphin A Inhibits Nociceptin-Converting Enzyme from the Rat Spinal Cord, Biochemical and Biophysical Research Communications, 287, 4, (927), (2001).
- Jolanta Kotlińska, Piotr Suder, Agnieszka Sciubisz, Anna Łęgowska, Julita Eilmes, Krzysztof Rolka and Jerzy Silberring, C-Terminal glycine is crucial for hyperalgesic activity of nociceptin/orphanin FQ-(1–6), European Journal of Pharmacology, 419, 1, (33), (2001).
- Michel Dumont and Simon Lemaire, Interactions of Dynorphin A-(1–13) and Nociceptin with Cardiac D2 Binding Sites: Inhibition of Ischemia-evoked Release of Noradrenaline from Synaptosomal–mitochondrial Fractions, Journal of Molecular and Cellular Cardiology, 32, 8, (1567), (2000).
- Sharon R. Letchworth, John P. Mathis, Grace C. Rossi, Richard J. Bodnar and Gavril W. Pasternak, Autoradiographic localization of125I[Tyr14]orphanin FQ/nociceptin and125I[Tyr10]orphanin FQ/nociceptin(1-11) binding sites in rat brain, The Journal of Comparative Neurology, 423, 2, (319), (2000).