CHARACTERIZATION OF RECEPTORS FOR FMRFAMIDE RELATED NEUROPEPTIDES

FMRF酰胺相关神经肽受体的表征

• 批准号: 3845355
• 负责人: K PAYZA
• 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/3845355
• 关键词: animal tissue; biological signal transduction; cell membrane; drug tolerance; guanine nucleotide binding protein; inhibitor /antagonist; laboratory rat; magnesium; morphine; narcotic antagonists; neuropeptide receptor; neuropeptides; peptide analog; radioimmunoassay; radiotracer; receptor binding; receptor coupling; sodium; spinal cord mapping

Neuropeptide FF (NPFF) is the mammalian homolog in the family of peptides related to the molluscan peptide FMRFamide. NPFF has been implicated as an anti-opiate peptide in morphine analgesia, and in the development of tolerance, dependence. and withdrawal. A binding assay for NPFF receptors was developed in membrane preparations of rat brain and spinal cord. The NPFF analog 125I-YLFQPQRFa bound specifically with 0.08 nM affinity to a single population of sites in spinal cord membranes. NPFF receptors were found to be regulated by sodium and magnesium ions and GTP. We found that NPFF receptor binding was highest in brain regions high in NPFF, and the levels of binding in saline-treated and morphine-dependent rats were not different. The NPFF analog daY8Ra reduced morphine tolerance in rats. These results may have implications in treatment of drug addiction and chronic pain. The proposed course of this project includes (1) study of SAR of peptide binding to NPFF receptors, (2) investigation of the coupling of NPFF receptors to cellular signal transduction systems, (3) development of specific NPFF antagonists, and (4) solubilization and purification of NPFF and FMRFamide receptors.

神经肽Ff(NPFf)是多肽家族中的哺乳动物同系物 与软体动物多肽FMRFamide有关。NPFF被牵连为 一种抗阿片肽在吗啡镇痛中的作用，以及在吗啡的发展中的作用 宽容，依赖。和戒烟。NPFF的结合试验 大鼠脑膜和脊髓膜上的受体 电源线。与0.08 nm特异结合的NPFF模拟125I-YLFQPQRFa 对脊髓膜中的单个部位具有亲和力。NPFF 研究发现，受体受钠离子和镁离子的调节 GTP。我们发现NPFF受体在大脑区域的结合率最高 NPFF含量较高，盐水组和对照组的结合水平 吗啡依赖大鼠也没有不同。NPFF模拟DAY8Ra 降低大鼠对吗啡的耐受性。这些结果可能会产生影响 治疗药物成瘾和慢性疼痛。 本课题的研究内容包括：(1)多肽的构效关系研究 与NPFF受体的结合，(2)NPFF偶联的研究 细胞信号转导系统的受体，(3)发展 以及(4)增溶和纯化 NPFF和FMRFamide受体。