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

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 tr uncated 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 antinocicepti on up to 10 min after injection, followed by a hyperalgesia. The analgesic effect was blocked by naloxone and hyperalgesia was inhibited by NMDA-and N MDA/glycine site antagonists. The results indicate that shorter nociceptin fragments still possess their biologic activity though possibly acting via receptors other than ORL1. (C) 1999 Elsevier Science Inc. All rights reserv ed.