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  • Title: Effect of nociceptin and [Phe1psi (CH2-NH) Gly2]-nociceptin-(1-13)-NH2 on tonic activity of rat hypothalamic neurons.
    Author: Yakimova KS, Pierau FK.
    Journal: Neurosci Lett; 1999 Oct 22; 274(2):87-90. PubMed ID: 10553944.
    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.
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