title: Opposite effects of neuropeptide FF on central antinociception induced by endomorphin-1 and endomorphin-2 in mice.
abstract: Neuropeptide FF (NPFF) is known to be an endogenous opioid-modulating peptide. Nevertheless, very few researches focused on the interaction between NPFF and endogenous opioid peptides. In the present study, we have investigated the effects of NPFF system on the supraspinal antinociceptive effects induced by the endogenous µ-opioid receptor agonists, endomorphin-1 (EM-1) and endomorphin-2 (EM-2). In the mouse tail-flick assay, intracerebroventricular injection of EM-1 induced antinociception via µ-opioid receptor while the antinociception of intracerebroventricular injected EM-2 was mediated by both µ- and κ-opioid receptors. In addition, central administration of NPFF significantly reduced EM-1-induced central antinociception, but enhanced EM-2-induced central antinociception. The results using the selective NPFF1 and NPFF2 receptor agonists indicated that the EM-1-modulating action of NPFF was mainly mediated by NPFF2 receptor, while NPFF potentiated EM-2-induecd antinociception via both NPFF1 and NPFF2 receptors. To further investigate the roles of µ- and κ-opioid systems in the opposite effects of NPFF on central antinociception of endomprphins, the µ- and κ-opioid receptors selective agonists DAMGO and U69593, respectively, were used. Our results showed that NPFF could reduce the central antinociception of DAMGO via NPFF2 receptor and enhance the central antinociception of U69593 via both NPFF1 and NPFF2 receptors. Taken together, our data demonstrate that NPFF exerts opposite effects on central antinociception of endomorphins and provide the first evidence that NPFF potentiate antinociception of EM-2, which might result from the interaction between NPFF and κ-opioid systems.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Zi-long
authors.initials: ZL
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Zheng-lan
authors.initials: ZL
authors.lastname: Han
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Jia-xin
authors.initials: JX
authors.lastname: Pan
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Xu-hui
authors.initials: XH
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Hong-hai
authors.initials: HH
authors.lastname: Tang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Chang
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, and Institute of Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D059225:Nociception / Q000187:drug effects*; D009842:Oligopeptides / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology
chemical_list: D044482:Benzeneacetamides; D004151:Dipeptides; D009842:Oligopeptides; D011759:Pyrrolidines; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C105293:endomorphin 1; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C051844:norbinaltorphimine; C105294:endomorphin 2; D009271:Naltrexone; C024524:beta-funaltrexamine; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; C055382:naltrindole; C045444:U 69593; D000218:Adamantane
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