Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor

• Published in: Science (American Association for the Advancement of Science) 1995-11, Vol.270 (5237), p.792-794
• Main Authors: Reinscheid, Rainer K., Nothacker, Hans-Peter, Bourson, Anne, Ardati, Ali, Henningsen, Robert A., Bunzow, James R., Grandy, David K., Langen, Hanno, Monsma, Frederick J., Civelli, Olivier
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclase Inhibitors; Amino Acid Sequence; Analgesics - pharmacology; Animals; Biochemistry and metabolism; Biological and medical sciences; Central nervous system; CHO Cells; Colforsin - pharmacology; Cricetinae; Dosage; Fundamental and applied biological sciences. Psychology; G proteins; GTP-Binding Proteins - metabolism; Hypothalamus - chemistry; Injections, Intraventricular; Injections, Spinal; Ligands; Mice; Molecular Sequence Data; Motor Activity - drug effects; Neuropeptides; Nociceptin; Opioid peptides; Opioid Peptides - chemistry; Opioid Peptides - isolation & purification; Opioid Peptides - metabolism; Opioid Peptides - pharmacology; Opioid receptors; Opioids; Orphans; Pain Measurement; Receptors; Receptors, Neuropeptide - metabolism; Receptors, Opioid - metabolism; String theory; Swine; Transfection; Vertebrates: nervous system and sense organs
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.270.5237.792

A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC 132) that is similar in sequence to opioid receptors. This peptide, orphanin FQ, has a primary structure reminiscent of that of opioid peptides. Nanomolar concentrations of orphanin FQ inhibited forskolin-stimulated adenylyl cyclase activity in cells transfected with LC132. This inhibitory activity was not affected by the addition of opioid ligands, nor did the peptide activate opioid receptors. Orphanin FQ bound to its receptor in a saturable manner and with high affinity. When injected intracerebroventricularly into mice, orphanin FQ caused a decrease in locomotor activity but did not induce analgesia in the hot-plate test. However, the peptide produced hyperalgesia in the tail-flick assay. Thus, orphanin FQ may act as a transmitter in the brain by modulating nociceptive and locomotor behavior.