Characterization of rat prepro-orphanin FQ/nociceptin(154-181): Nociceptive supraspinal sites Journal Article
| Authors: | Rossi, G. C.; Pellegrino, M.; Shane, R.; Abbadie, C. A.; Dustman, J.; Jimenez, C.; Bodnar, R. J.; Pasternak, G. W.; Allen, R. G. |
| Article Title: | Characterization of rat prepro-orphanin FQ/nociceptin(154-181): Nociceptive supraspinal sites |
| Abstract: | Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/K3-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 vIPAG 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 vIPAG 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. |
| Keywords: | controlled study; dose response; nonhuman; animals; animal tissue; carboxy terminal sequence; animal experiment; dose-response relationship, drug; protein processing; amino terminal sequence; brain; peptide fragments; peptide fragment; locus ceruleus; rat; ligand; amino acid; rats; rats, sprague-dawley; analgesics, opioid; pain measurement; cannula; brain region; peptide synthesis; hyperalgesia; nociception; naloxone; opiate receptor; reaction time; nociceptors; amygdala; opioid peptides; antinociception; radioimmunoassay; nociceptin; amygdaloid nucleus; medulla oblongata; periaqueductal gray matter; locus coeruleus; periaqueductal gray; narcotic antagonists; male; priority journal; article |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 300 |
| Issue: | 1 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2002-01-01 |
| Start Page: | 257 |
| End Page: | 264 |
| Language: | English |
| DOI: | 10.1124/jpet.300.1.257 |
| PUBMED: | 11752124 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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