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Research ArticleNEUROPHARMACOLOGY

Characterization of Rat Prepro-Orphanin FQ/Nociceptin(154–181): Nociceptive Processing in Supraspinal Sites

Grace C. Rossi, Michael Pellegrino, Randi Shane, Catherine A. Abbadie, Jessica Dustman, Charles Jimenez, Richard J. Bodnar, Gavril W. Pasternak and Richard G. Allen
Journal of Pharmacology and Experimental Therapeutics January 2002, 300 (1) 257-264; DOI: https://doi.org/10.1124/jpet.300.1.257
Grace C. Rossi
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Michael Pellegrino
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Randi Shane
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Catherine A. Abbadie
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Jessica Dustman
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Charles Jimenez
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Richard J. Bodnar
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Gavril W. Pasternak
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Richard G. Allen
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Abstract

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/κ3-like opioid receptor clone, produces a variety of behavioral responses, including those associated with pronociception and antinociception. The OFQ/N precursor rattus-proOFQ (rppOFQ/N) contains several paired basic amino acids, which raises the possibility that post-translational processing can be responsible for the production of a number of additional biologically active peptide fragments. One of these putative peptides, rppOFQ/N (rppOFQ/N154–181), was examined for antinociceptive and pronociceptive processes in four brain sites involved in pain inhibition: the ventrolateral periaqueductal gray (vlPAG), the amygdala, the locus coeruleus (LC), and the rostroventromedial medulla (RVM). Endogenous rppOFQ/N154–181 was identified in each region. rppOFQ/N154–181 produced a dose-dependent antinociception in all four sites using the tailflick assay. Injections into misplaced cannula sites failed to exert effects. Antinociception in the four sites differed in their response to the opioid antagonist naloxone. Naloxone pretreatment completely blocked rppOFQ/N154–181-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N154–181 was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N154–181 also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N154–170, also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N174–181). Although both rppOFQ/N154–181 and rppOFQ/N154–170 produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N154–181 has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites.

Footnotes

  • Supported, in part, by Grant DA11282 (to R.G.A.), Grants DA02615 and DA07242, a Senior Scientist Award DA0220 (to G.W.P.), and Research Scientist Award DA00310 (to G.C.R.) from the National Institute on Drug Abuse.

  • Abbreviations

    rppOFQ/N
    rattus prepro-orphanin FQ/nociceptin
    rppOFQ/N154–181
    rattus prepro-orphanin FQ/nociceptin full-length peptide
    OFQ2
    prepro-orphanin FQ/N154–170 or beginning of full-length peptide
    rppOFQ/N174–181
    end of full-length peptide
    vlPAG
    ventrolateral periaqueductal gray
    PAG
    periaqueductal gray
    LC
    locus coeruleus
    RVM
    rostroventromedial medulla
    icv
    intracerebroventricularly
    RP-HPLC
    reverse phase-high-performance liquid chromatography
    • Received May 31, 2001.
    • Accepted August 13, 2001.
    • The American Society for Pharmacology and Experimental Therapeutics
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    Journal of Pharmacology and Experimental Therapeutics: 300 (1)
    Journal of Pharmacology and Experimental Therapeutics
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    1 Jan 2002
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    Research ArticleNEUROPHARMACOLOGY

    Characterization of Rat Prepro-Orphanin FQ/Nociceptin(154–181): Nociceptive Processing in Supraspinal Sites

    Grace C. Rossi, Michael Pellegrino, Randi Shane, Catherine A. Abbadie, Jessica Dustman, Charles Jimenez, Richard J. Bodnar, Gavril W. Pasternak and Richard G. Allen
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 257-264; DOI: https://doi.org/10.1124/jpet.300.1.257

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    Research ArticleNEUROPHARMACOLOGY

    Characterization of Rat Prepro-Orphanin FQ/Nociceptin(154–181): Nociceptive Processing in Supraspinal Sites

    Grace C. Rossi, Michael Pellegrino, Randi Shane, Catherine A. Abbadie, Jessica Dustman, Charles Jimenez, Richard J. Bodnar, Gavril W. Pasternak and Richard G. Allen
    Journal of Pharmacology and Experimental Therapeutics January 1, 2002, 300 (1) 257-264; DOI: https://doi.org/10.1124/jpet.300.1.257
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