Analgesic activity of orphanin FQ2, murine prepro-orphanin FQ141-157 in mice.
Orphanin FQ/nociceptin (OFQ/N) is generated from a larger precursor peptide, prepro-orphanin FQ (ppOFQ). Within the sequence of murine ppOFQ is another putative heptadecapeptide, orphanin FQ2 (OFQ2), corresponding to murine ppOFQ141-157. OFQ2 was a potent analgesic given either supraspinally (ED50 0.5 microgram, i.c.v.) or spinally (ED50 0.7 microgram, i.t.). As with opioids and OFQ/N, OFQ2 analgesia was enhanced by blockade of sigma receptors with haloperidol, which increased the potency of the peptide over 10-fold. Supraspinal OFQ2 analgesia was readily reversed by naloxone, implying that it activated opioid systems. Spinal OFQ2 analgesia was insensitive to naloxone. OFQ2 also inhibited gastrointestinal transit. Together, these studies suggest that OFQ2 may be a relevant neuropeptide with important physiological actions.
Rossi
G C
GC
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Mathis
J P
JP
Pasternak
G W
GW
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D000701:Analgesics, Opioid; D014150:Antipsychotic Agents; D006220:Haloperidol; D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000097629:Nociceptin; C113545:prepro-orphanin FQ(141-157)