Metabolic fate of nociceptin/orphanin FQ in the rat spinal cord and biological activity of its released fragment

Peptides. 1999;20(2):239-47. doi: 10.1016/s0196-9781(98)00165-x.


Metabolism of orphanin FQ/nociceptin (OFQ/N) was studied in the spinal cord of rats. The heptadecapeptide was efficiently cleaved by a neutral serine endopeptidase, thus releasing the major metabolite, OFQ/N(1-11), further truncated to the final product, OFQ/N(1-6). Biologic activity of this latter fragment was tested in vivo, after intracerebroventricular and intrathecal injections. Hexapeptide exhibited a bi-phasic effect, causing antinociception up to 10 min after injection, followed by a hyperalgesia. The analgesic effect was blocked by naloxone and hyperalgesia was inhibited by NMDA--and NMDA/glycine site antagonists. The results indicate that shorter nociceptin fragments still possess their biologic activity though possibly acting via receptors other than ORL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Male
  • Oligopeptides / pharmacology*
  • Opioid Peptides / metabolism*
  • Opioid Peptides / pharmacology*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Rats
  • Rats, Wistar
  • Serine Endopeptidases / isolation & purification
  • Spinal Cord / enzymology
  • Spinal Cord / metabolism*


  • Analgesics
  • Oligopeptides
  • Opioid Peptides
  • Peptide Fragments
  • nociceptin (1-11)
  • nociceptin (1-6)
  • nociceptin
  • Serine Endopeptidases