Central Administration of Neuropeptide FF and Related Peptides Attenuate Systemic Morphine Analgesia in Mice

Fang, Quan; Jiang, Tiannan; Li, Ning; Han, Zheng-lan; Wang, Rui

doi:10.2174/092986611794654012

Cited by 25 publications

(17 citation statements)

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“…Previously, a number of studies have shown that NPFF itself has no significant effect on nociceptive threshold but attenuates the central antinociception induced by endogenous or exogenous opioids after i.c.v. co‐administration (Roumy and Zajac, ; Fang et al , ; Li et al , ; Wang et al , ). In theory, BN‐9 containing both NPFF and opioid agonist activities could partially exert anti‐opioid activities of the NPFF moiety and reduce its antinociception after supraspinal administration.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports have shown that NPFF belongs to a neuropeptide family that includes two precursors (pro-NPFF A and pro-NPFF B ) and two GPCRs (NPFF1 and NPFF2) (Perry et al, 1997;Vilim et al, 1999;Bonini et al, 2000;Elshourbagy et al, 2000;Hinuma et al, 2000;Liu et al, 2001). There is mounting evidence indicating that NPFF has no effects on nociception alone and modulates opioid-induced antinociception differentially, depending on its site of administration (Roumy and Zajac, 1998;Panula et al, 1999;Fang et al, 2011). NPFF delivered by the i.c.v.…”

Section: Introductionmentioning

confidence: 99%

“…NPFF delivered by the i.c.v. route has been shown to block morphine-induced analgesia (Panula et al, 1999;Fang et al, 2011). In contrast, i.t.…”

Section: Introductionmentioning

confidence: 99%

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BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

Han

Wang

et al. 2016

British J Pharmacology

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BACKGROUND AND PURPOSENeuropeptide FF (NPFF) behaves as an endogenous opioid-modulating peptide. In the present study, the opioid and NPFF pharmacophore-containing chimeric peptide BN-9 was synthesized and pharmacologically characterized. EXPERIMENTAL APPROACHAgonist activities of BN-9 at opioid and NPFF receptors were characterized in in vitro cAMP assays. Antinociceptive activities of BN-9 were evaluated in the mouse tail-flick and formalin tests. Furthermore, its side effects were investigated in rotarod, antinociceptive tolerance, reward and gastrointestinal transit tests. KEY RESULTSBN-9 acted as a novel multifunctional agonist at μ, δ, κ, NPFF1 and NPFF2 receptors in cAMP assays. In the tail-flick test, BN-9 produced dose-related antinociception and was approximately equipotent to morphine; this antinociception was blocked by μ and κ receptor antagonists, but not by the δ receptor antagonist. In the formalin test, supraspinal administration of BN-9 produced significant analgesia. Notably, repeated administration of BN-9 produced analgesia without loss of potency over 8 days. In contrast, repeated i.c.v. co-administration of BN-9 with the NPFF receptor antagonist RF9 produced significant antinociceptive tolerance. Furthermore, i.c.v. BN-9 induced conditioned place preference. When given by the same routes, BN-9 had a more than eightfold higher ED 50 value for gastrointestinal transit inhibition compared with the ED 50 values for antinociception. CONCLUSIONS AND IMPLICATIONSBN-9 produced a robust, nontolerance-forming analgesia with limited inhibition of gastrointestinal transit. As BN-9 is able to activate both opioid and NPFF systems, this provides an interesting approach for the development of novel analgesics with minimal side effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

Han

Wang

et al. 2016

British J Pharmacology

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“…[35] The crude peptides were firstly desalted by Gel filtration, and then purified by preparative RP-HPLC using a Waters Delta 600 system coupled to a UV detector. Analytical RP-HPLC was used to establish the purity of those peptides.…”

Section: Methodsmentioning

confidence: 99%

Opposite Effects of Neuropeptide FF on Central Antinociception Induced by Endomorphin-1 and Endomorphin-2 in Mice

et al. 2014

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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.

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“…In mice, i.c.v. injection of VPNLPQRF-NH 2 (human RFRP-3) in the lateral ventricle has been reported to either potentiate morphine analgesia at high doses [10–32 nmol; ( 50 )] or decrease morphine analgesia at similar doses [20 nmol; ( 37 )]. Conversely, i.c.v.…”

Section: Npff Rfrp and Npff Receptors 1/2mentioning

confidence: 99%

Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents

Ayachi¹,

Simonin²

2014

Front. Endocrinol.

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Mammalian RF-amide peptides, which all share a conserved carboxyl-terminal Arg–Phe–NH2 sequence, constitute a family of five groups of neuropeptides that are encoded by five different genes. They act through five G-protein-coupled receptors and each group of peptide binds to and activates mostly one receptor: RF-amide related peptide group binds to NPFFR1, neuropeptide FF group to NPFFR2, pyroglutamylated RF-amide peptide group to QRFPR, prolactin-releasing peptide group to prolactin-releasing peptide receptor, and kisspeptin group to Kiss1R. These peptides and their receptors have been involved in the modulation of several functions including reproduction, feeding, and cardiovascular regulation. Data from the literature now provide emerging evidence that all RF-amide peptides and their receptors are also involved in the modulation of nociception. This review will present the current knowledge on the involvement in rodents of the different mammalian RF-amide peptides and their receptors in the modulation of nociception in basal and chronic pain conditions as well as their modulatory effects on the analgesic effects of opiates.

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Central Administration of Neuropeptide FF and Related Peptides Attenuate Systemic Morphine Analgesia in Mice

Cited by 25 publications

References 0 publications

BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

BN‐9, a chimeric peptide with mixed opioid and neuropeptide FF receptor agonistic properties, produces nontolerance‐forming antinociception in mice

Opposite Effects of Neuropeptide FF on Central Antinociception Induced by Endomorphin-1 and Endomorphin-2 in Mice

Involvement of Mammalian RF-Amide Peptides and Their Receptors in the Modulation of Nociception in Rodents

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