title: Effect of nociceptin and [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 on tonic activity of rat hypothalamic neurons.
abstract: The effect of nociceptin, an endogenous ligand for a unique member of the cloned opioid receptor family ORL1-receptor, on tonic activity of neurons in the preoptic area/anterior hypothalamus (PO/AH) has been examined in rat brain slices using extracellular recordings. Nociceptin (1, 10 and 100 nM) decreased dose-dependently tonic activity of PO/AH neurons. This effect was not significantly different from the effect of [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 (1, 10 and 100 nM), recently proposed as a selective antagonist of the nociceptin receptor. Thus, [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 appears to be an agonist rather than an antagonist of nociceptin (ORL1) receptor in rat PO/AH neurons. However, there was neither antagonism nor additive synergism when nociceptin and [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 were applied simultaneously at equimolar concentrations. The effect of nociceptin on tonic activity of rat PO/AH neurons was not blocked by selective mu-, kappa- and delta-opioid receptor antagonists (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine and naltrindol, respectively) at 10 times higher concentrations than nociceptin. These data suggest that the effect of nociceptin on tonic activity of PO/AH neurons is not due to an action on mu-, kappa-, or delta-opioid receptors but results from a specific effect on the ORL1-receptor.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Sofia, Bulgaria.
authors.forename: K S
authors.initials: KS
authors.lastname: Yakimova
authors.forename: F K
authors.initials: FK
authors.lastname: Pierau
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007031:Hypothalamus / Q000166:cytology* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D018847:Opioid Peptides; D010446:Peptide Fragments; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C114149:nociceptin (1-13)-NH2, Phe(1)-psi(CH2-NH)-Gly(2)-; C000722285:Oprl1 protein, rat