NEUROPEPTIDE FF (FLFQPQRF-NH2) IN BRAIN AND SPINAL CORD--FUNCTION & DISTRIBUTION

大脑和脊髓中的神经肽 FF (FLFQPQRF-NH2)——功能

• 批准号: 3845207
• 负责人: H-Y T YANG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3845207
• 关键词: adrenal glands; antiserum; brain; brain mapping; drug addiction; drug tolerance; drug withdrawal; endorphins; laboratory rat; molecular cloning; morphine; naloxone; neuropeptides; neuropharmacology; pancreas; pituitary gland; protein metabolism; spinal cord

Neuropeptide FF (FLFQPQRF-NH2) was originally isolated from the bovine brain and found to have morphine modulating activity. Recently there are studies suggesting the involvement of neuropeptide FF (NPFF) in morphine abstinence and tolerance. In this study the role of endogenous NPFF in opiate dependence was further assessed using NPFF antibody as a specific antagonist. Rats, which were rendered dependent to opiate by morphine pellets, simultaneously received icv infusions of anti-NPFF IgG or control IgG. Naloxone induced abstinence signs were significantly lower in the group treated with anti-NPFF IgG than the group treated with control IgG. NPFF is highly localized in nerve terminals in the posterior pituitary. Superfusion of posterior lobes of rat pituitaries demonstrated that NPFF can be released from the pituitary by depolarizing concentration of KCI. Using this posterior pituitary as a model, we have found that naloxone can cause a significant release of NPFF from the pituitary of the rat pretreated with morphine. The amounts of NPFF released seem to increase with increasing dose and duration of the morphine treatment. The results strongly indicate that release of NPFF may participate in the naloxone precipitated opiate withdrawal. In order to further study the possible role of NPFF in opiate withdrawal and tolerance, work was initiated to attempt to isolate a specific cDNA clone for NPFF precursor protein. We are also currently isolating other NPFF-like peptides from adrenal and pancreatic glands with the aim of characterizing them both chemically and biologically.

神经肽FF（FLIPQRF-NH 2）最初分离自牛 大脑，并发现具有吗啡调节活性。 最近有 研究表明神经肽FF（NPFF）参与吗啡 禁欲和宽容 在这项研究中，内源性NPFF的作用， 使用NPFF抗体作为特异性抗体， 拮抗剂 用吗啡使大鼠产生阿片依赖 颗粒，同时接受抗NPFF IgG的icv输注或 对照IgG。 纳洛酮诱导的戒断体征明显降低 在用抗NPFF IgG处理的组中， 对照IgG。 NPFF高度定位于神经末梢， 垂体后叶 大鼠垂体后叶的灌流 证明NPFF可以通过去极化从垂体释放 KCl浓度。 以这个垂体后叶为模型， 发现纳洛酮可以引起NPFF从 吗啡预处理大鼠垂体。 NPFF的数量 释放的似乎随着剂量和持续时间的增加而增加 吗啡治疗 结果强烈表明，NPFF的释放 可能参与纳洛酮促阿片戒断。 为了 进一步研究NPFF在阿片戒断中的可能作用， 耐受性，开始工作以尝试分离特定cDNA克隆 NPFF前体蛋白。 我们目前也在隔离其他 来自肾上腺和胰腺的NPFF样肽，目的是 从化学和生物学上对它们进行鉴定。