Identification of a high-affinity orphanin FQ/nociceptin(1-11) binding site in mouse brain Journal Article
| Authors: | Mathis, J. P.; Goldberg, I. E.; Letchworth, S. R.; Ryan-Moro, J. P.; Pasternak, G. W. |
| Article Title: | Identification of a high-affinity orphanin FQ/nociceptin(1-11) binding site in mouse brain |
| Abstract: | 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), [125I][Tyr10]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 [125I] [Tyr10] 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 [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. |
| Keywords: | nonhuman; binding affinity; mouse; animals; mice; animal tissue; opiate; protein binding; mice, inbred strains; amino acid sequence; brain; binding site; binding sites; opioid; vasodilator agents; autoradiography; fentanyl; opiate receptor; naltrindole; opioid peptides; cyclazocine; naloxone benzoylhydrazone; nociceptin; brain chemistry; levallorphan; radioligand assay; narcotics; receptors, opioid; alpha neoendorphin; priority journal; article; diprenorphine; nociceptin receptor; dynorphins; orphanin fq; kor-3; dynorphin a derivative |
| Journal Title: | Synapse |
| Volume: | 34 |
| Issue: | 3 |
| ISSN: | 0887-4476 |
| Publisher: | John Wiley & Sons |
| Date Published: | 1999-12-01 |
| Start Page: | 181 |
| End Page: | 186 |
| Language: | English |
| DOI: | 10.1002/(sici)1098-2396(19991201)34:3<181::aid-syn2>3.0.co;2-v |
| PUBMED: | 10523755 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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