CHARACTERIZATION OF RECEPTORS FOR FMRFAMIDE RELATED NEUROPEPTIDES

神经肽FF（neuropeptide FF，NPFF）是肽家族中的哺乳动物同源物 与软体动物肽FMRFamide相关。 NPFF被牵连， 一种抗阿片肽，用于吗啡镇痛， 宽容依赖和撤退。 NPFF的结合测定 在大鼠脑和脊髓膜制备物中， 线. NPFF类似物125 I-YLQRFa与0.08 nM的NPFF特异性结合。 对脊髓膜中单个位点群体的亲和力。 NPFF 发现受体受钠和镁离子的调节， GTP 我们发现NPFF受体结合在大脑区域最高 高NPFF，以及盐水处理和 吗啡依赖的大鼠没有什么不同。 NPFF模拟物daY 8 Ra 降低大鼠的吗啡耐受性。 这些结果可能会对 用于治疗毒瘾和慢性疼痛。 本课题的研究内容包括：（1）多肽分子的构效关系研究 与NPFF受体的结合，（2）NPFF的偶联研究 受体的细胞信号转导系统，（3）发展 特异性NPFF拮抗剂，和（4）溶解和纯化 NPFF和FMRFamide受体。

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.