Peripheral orphanin FQ/nociceptin analgesia in the mouse.
Orphanin FQ/Nociceptin (OFQ/N) administered peripherally was an effective analgesic in the tailflick test in mice (ED50 16.3 microg). It had a peak effect at 5 min and lasted up to 30 min. The kappa3 analgesic naloxone benzoylhydrazone was also active peripherally (ED50 3.8 microg). The analgesic actions of both agents were blocked by naloxone. Neither OFQ/N(1-11) nor OFQ/N(1-7) had appreciable peripheral activity. Antisense mapping both compounds against the murine orphan opioid receptor (KOR-3) confirmed the importance of this clone in their actions. Antisense probes targeting the second and third coding exons significantly lowered the analgesic effects of both compounds. However, the antisense targeting the first coding exon blocked only the actions of OFQ/N and not kappa3 analgesia.
Kolesnikov
Y A
YA
The Cotzias Laboratory of Neuro-Oncology and The Department of Anesthesiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Pasternak
G W
GW
D000698:Analgesia; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D005091:Exons; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D018847:Opioid Peptides / Q000008:administration & dosage* / Q000378:metabolism; D010147:Pain Measurement; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000701:Analgesics, Opioid; D016375:Antisense Elements (Genetics); D009270:Naloxone; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C058380:naloxone benzoylhydrazone; C000722287:Oprl1 protein, mouse