| Carboxyl terminal peptides derived from prepro-orphanin FQ/nociceptin (ppOFQ/N) are produced in the hypothalamus and possess analgesic bioactivities. | |
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MedLine Citation:
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PMID: 11259764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the ORL-1/KOR-3 receptor, produces a wide variety of behavioral responses. Its precursor protein, prepro-OFQ/N (ppOFQ/N) contains several series of amino acids bounded by pairs of basic amino acids, raising the possibility that additional functional neuropeptides could be generated by proteolytic posttranslational processing. Several of these processing products have been shown to have pharmacological activity, including the 17 amino acid peptide OFQ/N (mppOFQ/N(140-157)) which is a major product of this precursor in the hypothalamus. Here we have used a newly developed radioimmunoassay and RP-HPLC to detect mppOFQ/N(160-187) in mouse hypothalamic extracts. Murine ppOFQ/N(160-187) has potent analgesic activity supraspinally (3.4 nmol, i.c.v.) and spinally (4.3 nmol, i.t.). This analgesic activity was reversed by the opioid antagonist naloxone (5 mg/kg, s.c.) and kappa(1)-selective opioid antagonist nor-BNI (60 microg, i.c.v.), despite the inability of ppOFQ/N(160-187) to compete binding in mu, delta, kappa(1), kappa(3), or OFQ/N binding assays. These findings suggest that murine ppOFQ/N(160-187) may be a physiologically relevant neuropeptide with a novel mechanism of action. |
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Authors:
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J P Mathis; G C Rossi; M J Pellegrino; C Jimenez; G W Pasternak; R G Allen |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Brain research Volume: 895 ISSN: 0006-8993 ISO Abbreviation: Brain Res. Publication Date: 2001 Mar |
Date Detail:
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Created Date: 2001-03-22 Completed Date: 2001-07-19 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 89-94 Citation Subset: IM |
Affiliation:
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The Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence
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physiology Analgesics, Opioid / pharmacology* Animals Dose-Response Relationship, Drug Hypothalamus / drug effects, metabolism* Mice Molecular Sequence Data Narcotic Antagonists / pharmacology Opioid Peptides / analysis*, chemistry, metabolism*, pharmacology* Pain / drug therapy*, metabolism, physiopathology Pain Threshold / drug effects, physiology Peptide Fragments / analysis*, chemistry, pharmacology* Protein Structure, Tertiary / physiology Radioimmunoassay* Receptors, Opioid / drug effects, metabolism Sequence Homology, Amino Acid Spinal Cord / drug effects, physiology |
| Grant Support | |
ID/Acronym/Agency:
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CA08748/CA/NCI NIH HHS; DA00220/DA/NIDA NIH HHS; DA00310/DA/NIDA NIH HHS; DA02615/DA/NIDA NIH HHS; DA07242/DA/NIDA NIH HHS; DA11282/DA/NIDA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Opioid; 0/Narcotic Antagonists; 0/Opioid Peptides; 0/Peptide Fragments; 0/Receptors, Opioid; 0/nociceptin; 0/prepro-orphanin FQ(141-157); 0/prepro-orphanin FQ(160-187) |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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