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

TLDR

A heptadecapeptide isolated from porcine brain, orphanin FQ, binds to the LC132 G protein‑coupled receptor, which is structurally related to opioid receptors, and its sequence resembles opioid peptides. The study sought to determine whether orphanin FQ acts as a brain transmitter by modulating nociceptive and locomotor behavior. Orphanin FQ binds LC132 with high affinity, inhibits forskolin‑stimulated adenylyl cyclase, reduces locomotor activity without producing analgesia, and induces hyperalgesia in the tail‑flick assay, suggesting it modulates pain and movement.

Abstract

A heptadecapeptide was identified and purified from porcine brain tissue as a ligand for an orphan heterotrimeric GTP- binding protein (G protein)- coupled receptor (LC132) 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.