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

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 opi...

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Veröffentlicht in:Science (American Association for the Advancement of Science) 1995-11, Vol.270 (5237), p.792-794
Hauptverfasser: 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
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container_issue 5237
container_start_page 792
container_title Science (American Association for the Advancement of Science)
container_volume 270
creator 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
description 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.
doi_str_mv 10.1126/science.270.5237.792
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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
title Orphanin FQ: A Neuropeptide that Activates an Opioidlike G Protein-Coupled Receptor
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