Orphanin FQ is a functional anti-opioid peptide.
The heptadecapeptide orphanin FQ has recently been shown to be the endogenous agonist for the orphan opioid-like receptor, LC132. The molecular evidence that LC132 and orphanin FQ are evolutionarily related to other opioid receptors and their ligands suggests that these proteins may also play a role in modulating opiate actions. We now report that orphanin FQ (0.5-10 nmol), injected intracerebroventricularly in mice, does not produce hyperalgesia as suggested previously but rather reverses opioid-mediated (i.e. naloxone-sensitive) stress-induced antinociception in three different algesiometric assays. In addition to its antagonism of endogenous opioid antinociception, orphanin FQ dose-dependently (2.5-25 nmol) reverses systemic morphine antinociception (5 mg/kg, s.c.). Based on these data, we propose that orphanin FQ is a functional anti-opioid peptide.
Mogil
J S
JS
Research Service, VA Medical Center, Portland, OR 97201, USA.
Grisel
J E
JE
Reinscheid
R K
RK
Civelli
O
O
Belknap
J K
JK
Grandy
D K
DK
D000085:Acetates; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement; D013315:Stress, Psychological / Q000150:complications; D000097629:Nociceptin
D000085:Acetates; D000701:Analgesics, Opioid; D009020:Morphine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D000097629:Nociceptin