Nociceptin Opioid Peptide Research Articles

An investigation of binding sites for paracetamol in the mouse brain and spinal cord

Quantitative autoradiography has been used to assess whether [ 3H]paracetamol (3 μM) binds specifically to any area of the murine brain and spinal cord and to investigate whether paracetamol (1–100 μM) competes for binding to the nociceptin opioid peptide (NOP) receptor or to the nitrobenzylthioinosine (NBTI)-sensitive adenosine transporter in the brains of mice. [ 3H]paracetamol binding was homogenous and, although there was some indication of specific binding overall, this binding in most individual regions failed to reach statistical significance. However, thoracic segments of the spinal cord were found to have significantly higher specific binding than cervical and lumbar regions. Paracetamol did not significantly compete for binding to the NOP receptor or to the NBTI-sensitive adenosine transporter, showing that it does not mediate its effect via these sites. Although paracetamol did bind specifically to the murine brain and spinal cord, the binding was not region-specific, suggesting binding is not related to any particular neurotransmitter system.

Inhibition of nociceptin/orphanin FQ on penicillin-induced seizures in rats

The opioid peptides were thought to be involved in specific types of seizures. Nociceptin/Orphanin FQ (NC) is the endogenous ligand of the nociceptin opioid peptide (NOP) receptor and may play a role in epilepsy. However, accumulated evidences indicated that NC had both anti- and pro-convulsive effects, and the direct effect of NC in modulating epilepsy in the hippocampus still remained unclear. In this study, we investigated the effect of NC on penicillin-induced seizures (PIS) in rats. Seizure model was produced by intra-hippocampus injection of penicillin in anesthetized rats. The electroencephalography (EEG) was then observed and estimated by power spectrum analysis. Pretreatment of NC (intracerebroventricular, i.c.v.) depressed PIS in a dose-dependent manner at doses of 0.055, 0.55 and 5.5 nmol in 2 μl saline, respectively. [Nphe 1]Nociceptin(1–13)NH 2, a selective NOP receptor antagonist reversed the effect of NC against PIS, and this antagonist was inactive to PIS itself. These results indicated that NC had a receptor-specific preventive effect against PIS.

Studies of G Protein Activation of Orphanin FQ in the Cerebrum, Thalamus and Spinal Cord of Monkeys

Background: The aim of this in vitro study was to investigate []GTPS binding stimulated activation by orphanin FQ in monkey cerebral, thalamic, and spinal membranes. Methods: A rhesus monkey (Macaca mulatta, female, n = 1) was euthanized to obtain cerebral, thalamic, and spinal cord membrane preparations. In the orphanin FQ-stimulated []GTPS binding dose-response curve, (effective concentration 50, nanomolar) and maximum stimulation (% over basal) were determined in the absence or presence of each opioid receptor antagonist, namely, naloxone (20 nM), nor-BNI (3 nM), naltrindole (3 nM), or J-113397 (10 nM) antagonists of the , and nociceptin- opioid receptors respectively. Results: The values of EC50 and maximum stimulation of []GTPS binding were as follows: cortex (5.1 1.4 nM / 55.6 8.2%), thalamus (8.5 [ 1.3 nM / 27.8 4.9%), and spinal cord (11.3 ﾘ 0.2 nM / 15.2 4.5%). Maximum stimulation for these three membranes were significantly different (P ]GTPS binding dose-response curve, but the other opioid receptor antagonists had no effect. Conclusions: Maximum stimulation of []GTPS binding by OFQ in each membrane showed significantly different profiles, suggesting different pharmacologic efficacies by region. The OFQ-stimulated []GTPS bindings in this study were mediated via nociceptin-opioid peptide receptor stimulation.

Feeding induced by food deprivation is differentially reduced by opioid receptor antisense oligodeoxynucleotide probes in rats

The increases in food intake following 24 h of food deprivation are reduced by systemic and central administration of general opioid antagonists. The use of selective opioid antagonists revealed that μ-selective antagonists were more effective than κ-selective antagonists in reducing deprivation-induced intake, whereas δ-selective antagonists were minimally effective. Antisense oligodeoxynucleotide (AS ODN) probes directed against different exons of the μ (MOP), δ (DOP), κ (KOP) and nociceptin (NOP) opioid peptide receptor genes have been able to differentially alter feeding responses elicited by glucoprivation, lipoprivation and by different opioid peptides and receptor agonists. The present study examined whether lateral ventricular administration of AS ODN probes directed against different exons of the MOP, DOP, KOP or NOP opioid receptor genes altered food intake and body weight changes following 24 h of food deprivation in rats. Deprivation-induced feeding was significantly and maximally reduced by an AS ODN probe directed against exon 2, but not exons 1 or 3 of the KOP gene. This response was also significantly though modestly reduced by AS ODN probes directed against exons 2, 3 or 4 of the MOP gene, exon 1 of the DOP gene, or exon 1 of the NOP gene. Recovery of body weight following postdeprivation food reintroduction was significantly reduced by AS ODN probes directed against either exons 2, 3 or 4 of the MOP gene, exons 1 or 2 of the DOP gene, or exons 1, 2 or 3 of the KOP gene. The parallel patterns in the magnitude of alterations in deprivation-induced feeding by δ antagonists and DOP AS ODN probes on one hand, and by κ antagonists and KOP AS ODN probes on the other, provide converging and complementary evidence for their relative involvement in this response. The modest reductions by MOP AS ODN probes relative to the more potent reductions induced by μ-selective antagonists suggest that the μ receptor-mediated actions upon deprivation-induced feeding may involve recently-identified splice variants or isoforms of the MOP gene.

Nociceptin inhibits acquisition of amphetamine-induced place preference and sensitization to stereotypy in rats

Nociceptin (also called orphanin FQ), a 17-amino-acid peptide, is the natural ligand of the nociceptin opioid peptide (NOP) receptor. This peptide shows similarities, in its structure, to opioid peptides, mainly to dynorphin A. However, unlike opioid peptides, it does not produce a conditioned place preference or aversion but inhibits rewarding effect of drugs of abuse. The present study was designed to examine the ability of nociceptin to block the acquisition of amphetamine-induced place preference, and the development of amphetamine-induced sensitization to stereotypy in rats. Our experiments indicated that repeated administration of nociceptin at increasing doses during conditioning significantly attenuated the reinforcing effect of amphetamine in conditioned place preference paradigm. Nociceptin did not change the acute effect of amphetamine-induced stereotypy but prevented the development of sensitization to stereotypy measured on the challenge day. Our results suggest the involvement of nociceptin in long-lasting neuronal adaptation after repeated amphetamine treatment.