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Nociceptin/orphanin fq metabolism and bioactive metabolites

Academic Article
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Overview

authors

  • Terenius, Lars
  • Sandin, J.
  • Sakurada, T.

publication date

  • July 2000

journal

  • Peptides  Journal

abstract

  • The endogenous ligand for the orphan NOR receptor (earlier named ORL1) was recently discovered. This ligand, nociceptin/orphanin FQ is involved in a number of pharmacological actions in the CNS, including modulation of pain and cognition. However, its specific physiological role remains to be determined. Two major pathways of metabolism have been identified; the action of aminopeptidase(s) that prominently occurs in plasma, and endopeptidase activity that successively generates the N-terminal 1-13 and 1-9 fragments. Both pathways result in fragments that are inactive at the NOR receptor. However, short N-terminal fragments appear to be active in blocking the release of substance P from primary afferent C-fiber terminals in the dorsal spinal cord. The same endopeptidase(s) may also be involved in the fragmentation of dynorphin A since the inhibitor profile is similar. Enzyme activity is upregulated by morphine using either peptide as substrate that may lead to pharmacological interactions.

subject areas

  • Amino Acid Sequence
  • Aminopeptidases
  • Animals
  • Brain
  • Cell Line
  • Cells, Cultured
  • Dynorphins
  • Humans
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Opioid Peptides
  • Peptides
  • Protein Precursors
  • Rats
  • Receptors, Opioid
  • Spinal Cord
  • Tumor Cells, Cultured
  • Vasodilator Agents
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Identity

International Standard Serial Number (ISSN)

  • 0196-9781

Digital Object Identifier (DOI)

  • 10.1016/s0196-9781(00)00228-x

PubMed ID

  • 10998525
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Additional Document Info

start page

  • 919

end page

  • 922

volume

  • 21

issue

  • 7

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