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 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.
Suder
P
P
Faculty of Chemistry, Jagiellonian University, Krakow, Poland.
Kotlinska
J
J
Smoluch
M T
MT
Sällberg
M
M
Silberring
J
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000378:metabolism* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012697:Serine Endopeptidases / Q000302:isolation & purification; D013116:Spinal Cord / Q000201:enzymology / Q000378:metabolism*; D000097629:Nociceptin
D000700:Analgesics; D009842:Oligopeptides; D018847:Opioid Peptides; D010446:Peptide Fragments; D012697:Serine Endopeptidases; D000097629:Nociceptin; C121233:nociceptin (1-11); C121232:nociceptin (1-6)