Neuropeptide FF prevented histamine- or chloroquine-induced acute itch behavior through non-NPFF receptors mechanism in male mice

IF 2.5 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Honghai Tang , Ting Zhang , Jiamin Feng , Mengna Zhang , Biao Xu , Qinqin Zhang , Ning Li , Nan Zhang , Quan Fang
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Abstract

The neuropeptide FF (NPFF) system regulates various physiological and pharmacological functions, particularly pain modulation. However, the modulatory effect of NPFF system on itch remains unclear. To investigate the modulatory effect and functional mechanism induced by NPFF system on acute itch, we examined the effects of supraspinal administration of NPFF and related peptides on acute itch induced by intradermal (i.d.) injection of histamine or chloroquine in male mice. Our results indicated that intracerebroventricular (i.c.v.) administration of NPFF dose-dependently prevented histamine- or chloroquine-induced acute itch behaviors. In addition, the modulatory effect of NPFF was not affected by the selective NPFF receptor antagonist RF9. Furthermore, we investigated the effects of NPVF and dNPA, the selective agonists of NPFF1 and NPFF2 receptors respectively, on the acute itch. The results demonstrated that both NPFF agonists effectively prevented acute itch induced by histamine or chloroquine in a manner similar to NPFF, and their effects were also not modified by RF9. To further investigate the possible mechanism of the NPFF receptors agonists, the NPFF-derived analogues [Phg8]-NPFF and NPFF(1–7)-NH2 that could not activate NPFF receptors in cAMP assays were subsequently tested in the acute itch model. Interestingly, [Phg8]-NPFF, but not NPFF(1–7)-NH2, prevented acute itch behavior after i.c.v. administration. In conclusion, our findings reveal that NPFF and related peptides prevent histamine- and chloroquine-induced acute itch through a NPFF receptor-independent mechanism. And it was revealed that the C-terminal phenyl structure of NPFF may play a crucial role in these modulatory effects on acute itch.
神经肽 FF 通过非 NPFF 受体机制防止雄性小鼠出现组胺或氯喹诱发的急性瘙痒行为
神经肽 FF(NPFF)系统调节各种生理和药理功能,尤其是疼痛调节功能。然而,NPFF系统对痒的调节作用仍不清楚。为了研究 NPFF 系统对急性瘙痒的调节作用和功能机制,我们研究了在雄性小鼠皮内注射组胺或氯喹引起的急性瘙痒时,椎上注射 NPFF 和相关肽的影响。我们的研究结果表明,脑室内注射 NPFF 可剂量依赖性地阻止组胺或氯喹诱发的急性瘙痒行为。此外,NPFF的调节作用不受选择性NPFF受体拮抗剂RF9的影响。此外,我们还研究了 NPVF 和 dNPA(分别是 NPFF1 和 NPFF2 受体的选择性激动剂)对急性瘙痒的影响。结果表明,这两种NPFF受体激动剂都能有效地防止组胺或氯喹诱导的急性瘙痒,其作用方式与NPFF相似,而且RF9也不会改变它们的作用。为了进一步研究 NPFF 受体激动剂的可能机制,随后在急性瘙痒模型中测试了在 cAMP 试验中不能激活 NPFF 受体的 NPFF 衍生类似物 [Phg8]-NPFF 和 NPFF(1-7)-NH2。有趣的是,[Phg8]-NPFF(而非 NPFF(1-7)-NH2)在静脉注射后能防止急性瘙痒行为。总之,我们的研究结果表明,NPFF 和相关肽通过一种与 NPFF 受体无关的机制防止组胺和氯喹引起的急性瘙痒。研究还发现,NPFF 的 C 端苯基结构可能在这些对急性瘙痒的调节作用中发挥了关键作用。
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来源期刊
Neuropeptides
Neuropeptides 医学-内分泌学与代谢
CiteScore
5.40
自引率
6.90%
发文量
55
审稿时长
>12 weeks
期刊介绍: The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.
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