Document Detail


Carboxyl terminal peptides derived from prepro-orphanin FQ/nociceptin (ppOFQ/N) are produced in the hypothalamus and possess analgesic bioactivities.
MedLine Citation:
PMID:  11259764     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J P Mathis; G C Rossi; M J Pellegrino; C Jimenez; G W Pasternak; R G Allen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Brain research     Volume:  895     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-03-22     Completed Date:  2001-07-19     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  89-94     Citation Subset:  IM    
Affiliation:
The Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence / 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:
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:
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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