Nociceptin/orphanin FQ metabolism and bioactive metabolites

Peptides. 2000 Jul;21(7):919-22. doi: 10.1016/s0196-9781(00)00228-x.


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.

Publication types

  • Review

MeSH terms

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


  • Ligands
  • Opioid Peptides
  • Peptides
  • Protein Precursors
  • Receptors, Opioid
  • Vasodilator Agents
  • pronociceptin
  • Dynorphins
  • nociceptin
  • nociceptin receptor
  • Aminopeptidases