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

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.

[Nphe1]‐Nociceptin (1‐13)‐NH2, a nociceptin receptor antagonist, reverses nociceptin‐induced spatial memory impairments in the Morris water maze task in rats

“…Such changes in locomotor activity were detected in the ®rst 5 min of testing, and support the use of a 3 min testing period in the present study. However, this subject remains controversial with both decreases (Reinscheid et al, 1995;Devine et al, 1996;Sandin et al, 1997) and increases (Florin et al, 1996) in locomotion being reported. A possible explanation is related to doses, with lower doses of nociceptin inducing increased locomotor activity while higher doses decreased exploratory locomotor behaviour.…”

“…An endogenous agonist for OP 4 /nociceptin receptors was later identi®ed (Meunier et al, 1995;Reinscheid et al, 1995) and named orphanin FQ or nociceptin.…”

“…However, nociceptin is devoid of any activity at OP 1 , OP 2 or OP 3 opioid receptor subtypes (Meunier et al, 1995;Reinscheid et al, 1995). Since its discovery, a surge of scienti®c investigation has implicated a role for nociceptin in pain, fear and anxiety, feeding circadian rhythms (see Harrison & Grandy, 2000;Calo' et al, 2000b for recent reviews).…”

Neuropeptidomics: MS Applied to the Discovery of Novel Peptides from the Brain

“…The subtractive hybridization approach was used to discover the hypocretins and orexins, which are peptides that regulate feeding and wakefulness behavior (17 ). Orphan G-protein-coupled receptors (GPCRs) have been used as targets to identify and isolate their endogenous ligands, for example, nociceptin, the natural ligand for the opioid-like receptor (18,19).…”

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

“…The heptadecapeptide nociceptin/orphanin FQ is a recently discovered neuropeptide that exhibits structural homology with the opioid peptides and binds to an opioid-like G protein-coupled receptor (called OP 4 ) (Calo et al, 2000b;Meunier et al, 1995;Reinscheid et al, 1995). The neuroanatomical distribution of nociceptin/orphanin FQ and its receptor in brain areas known to play a role in the modulation of emotional processes (Anton et al, 1996) has led several groups to investigate the effects of central administration of nociceptin/orphanin FQ in anxiety models.…”