Premium
Identification of a high‐affinity orphanin FQ/nociceptin(1–11) binding site in mouse brain
Author(s) -
Mathis John P.,
Goldberg Ira E.,
Letchworth Sharon R.,
RyanMoro Jennifer P.,
Pasternak Gavril W.
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(19991201)34:3<181::aid-syn2>3.0.co;2-v
Subject(s) - nociceptin receptor , naltrindole , chemistry , diprenorphine , binding site , receptor , (+) naloxone , dynorphin , stereochemistry , opioid receptor , opioid peptide , opioid , biochemistry
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 (K i > 250 nM) for the OFQ/N receptor. Using an analog of OFQ/N(1–11), [ 125 I][Tyr 10 ]OFQ/N(1–11), we identified a high‐affinity binding site (K D 234 pM; B max 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 [ 125 I][Tyr 10 ]OFQ/N(1–11) binding in mouse brain with K i values below 10 nM, while naloxone benzoylhydrazone (K i 3.9 nM) labeled the [ 125 I][Tyr 10 ]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 [ 125 I][Tyr 10 ]OFQ/N(1–11) site had a unique regional distribution consistent with a distinct receptor. Thus, [ 125 I][Tyr 10 ]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.